Generic placeholder image

Current Traditional Medicine

Editor-in-Chief

ISSN (Print): 2215-0838
ISSN (Online): 2215-0846

Review Article

Anticancer Potential of Biologically Active Diosgenin and its Derivatives: An Update

Author(s): Sadhan Mondal*

Volume 10, Issue 1, 2024

Published on: 09 March, 2023

Article ID: e020223213390 Pages: 14

DOI: 10.2174/2215083809666230202143136

Price: $65

Abstract

Diosgenin (1) is an important steroidal metabolite often used as a precursor material for the synthesis of a broad array of steroidal drugs. Recent studies have indicated that compound (1) and many diosgenyl derivatives such as (1→9) possess both in vivo and in vitro biological activities like antioxidant, hypolipidemic, antithrombotic, immuno-modulatory, and estrogenic including anticancer activities. This steroidal sapogenin is of increasing interest in the pharmaceutical industry as it is being explored as an important starting material for the synthesis of oral contraceptives, sex hormones, and many other steroidal drugs having anticancer potential. Naturally occurring diosgenin, and its glucoside derivatives are quite abundant in several plant sources, but very little is known about the biogenesis of this class of secondary plant metabolites. Hence, designing a semi-synthetic protocol for the improved anticancer potential with enhanced efficacy of diosgenin and its derivatives is always a challenging field of cutting-edge research in pharmaceutical chemistry. The present review highlights some of the recent research findings and applications of this group of triterpenoids as a potential anticancer agent.

Keywords: Diosgenin, diosgenyl derivatives, bioavailability, biological activities, anticancer potential, steroidal sapogenin.

Graphical Abstract
[1]
Huang YX. Advance of diosgenin production processes. Shanghai J Tradit Chin Med 2004; 38: 56-8.
[2]
Qin TC, Zhang YD, Zhang JZ. Distribution and utilization of diosgenin resources in Hubei province. Biol Res 1997; 13: 200-2.
[3]
Liu P, Wu XY, Yue DY. Comprehensive utilization of diosgenin resources. Resour Econ Compr Util 1993; 12: 47-9.
[4]
Aradhana M, Rao AC, Kale RK. Diosgenin-a growth stimulator of mammary gland of ovariectomized mouse. Indian J Exp Biol 1992; 30(5): 367-70.
[PMID: 1459613]
[5]
Lepage C, Liagre B, Cook-Moreau J, Pinon A, Beneytout JL. Cyclooxygenase-2 and 5-lipoxygenase pathways in diosgenin-induced apoptosis in HT-29 and HCT-116 colon cancer cells. Int J Oncol 2010; 36(5): 1183-91.
[PMID: 20372792]
[6]
Chen PS, Shih YW, Huang HC, Cheng HW. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression. PLoS One 2011; 6(5)e20164
[http://dx.doi.org/10.1371/journal.pone.0020164] [PMID: 21629786]
[7]
Romero-Hernández LL, Merino-Montiel P, Montiel-Smith S, et al. Diosgenin-based thio(seleno)ureas and triazolyl glycoconjugates as hybrid drugs. Antioxidant and antiproliferative profile. Eur J Med Chem 2015; 99: 67-81.
[http://dx.doi.org/10.1016/j.ejmech.2015.05.018] [PMID: 26046314]
[8]
Huang BZ, Xin G, Ma LM, et al. Synthesis, characterization, and biological studies of diosgenyl analogs. J Asian Nat Prod Res 2017; 19(3): 272-98.
[http://dx.doi.org/10.1080/10286020.2016.1202240] [PMID: 27380052]
[9]
Masood-ur-Rahman. Mohammad Y, Fazili KM, Bhat KA, Ara T. Synthesis and biological evaluation of novel 3- O -tethered triazoles of diosgenin as potent antiproliferative agents. Steroids 2017; 118: 1-8.
[http://dx.doi.org/10.1016/j.steroids.2016.11.003] [PMID: 27864018]
[10]
Kim JK, Park SU. An update on the biological and pharmacological activities of diosgenin. EXCLI J 2018; 17: 24-8.
[PMID: 29383016]
[11]
Son IS, Kim JH, Sohn HY, Son KH, Kim JS, Kwon CS. Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats. Biosci Biotechnol Biochem 2007; 71(12): 3063-71.
[http://dx.doi.org/10.1271/bbb.70472] [PMID: 18071250]
[12]
Chiang SS, Chang SP, Pan TM. Osteoprotective effect of Monascus-fermented dioscorea in ovariectomized rat model of postmenopausal osteoporosis. J Agric Food Chem 2011; 59(17): 9150-7.
[http://dx.doi.org/10.1021/jf201640j] [PMID: 21800902]
[13]
Nie C, Zhou J, Qin X, et al. Diosgenin-induced autophagy and apoptosis in a human prostate cancer cell line. Mol Med Rep 2016; 14(5): 4349-59.
[http://dx.doi.org/10.3892/mmr.2016.5750] [PMID: 27667394]
[14]
Chaudhary S, Chaudhary PS, Chikara SK, Sharma MC, Iriti M. Review on fenugreek (Trigonella foenum-graecum L.) and its important secondary metabolite diosgenin. Not Bot Horti Agrobot Cluj-Napoca 2018; 46(1): 22-31.
[http://dx.doi.org/10.15835/nbha46110996]
[15]
Gong G, Qin Y, Huang W. Anti-thrombosis effect of diosgenin extract from Dioscorea zingiberensis C.H. Wright in vitro and in vivo. Phytomedicine 2011; 18(6): 458-63.
[http://dx.doi.org/10.1016/j.phymed.2010.08.015] [PMID: 21036572]
[16]
Huang CH, Liu DZ, Jan TR. Diosgenin, a plant-derived sapogenin, enhances regulatory T-cell immunity in the intestine of mice with food allergy. J Nat Prod 2010; 73(6): 1033-7.
[http://dx.doi.org/10.1021/np900690z] [PMID: 20465230]
[17]
Hsu KH, Chang CC, Tsai HD, Tsai FJ, Hsieh YY. Effects of yam and diosgenin on calpain systems in skeletal muscle of ovariectomized rats. Taiwan J Obstet Gynecol 2008; 47(2): 180-6.
[http://dx.doi.org/10.1016/S1028-4559(08)60077-7] [PMID: 18603503]
[18]
Yin J, Han N, Liu Z, Song S, Kadota S. The in vitro antiosteoporotic activity of some glycosides in Dioscorea spongiosa. Biol Pharm Bull 2010; 33(2): 316-20.
[http://dx.doi.org/10.1248/bpb.33.316] [PMID: 20118560]
[19]
Huang CH, Cheng JY, Deng MC, Chou CH, Jan TR. Prebiotic effect of diosgenin, an immunoactive steroidal sapogenin of the Chinese yam. Food Chem 2012; 132(1): 428-32.
[http://dx.doi.org/10.1016/j.foodchem.2011.11.016] [PMID: 26434311]
[20]
Manivannan J, Shanthakumar J, Arunagiri P, Raja B, Balamurugan E. Diosgenin interferes coronary vasoconstriction and inhibits osteochondrogenic transdifferentiation of aortic VSMC in CRF rats. Biochimie 2014; 102: 183-7.
[http://dx.doi.org/10.1016/j.biochi.2014.03.011] [PMID: 24742379]
[21]
Rajput S, Mandal M. Antitumor promoting potential of selected phytochemicals derived from spices. Eur J Cancer Prev 2012; 21(2): 205-15.
[http://dx.doi.org/10.1097/CEJ.0b013e32834a7f0c] [PMID: 21876437]
[22]
Srinivasan S, Koduru S, Kumar R, Venguswamy G, Kyprianou N, Damodaran C. Diosgenin targets Akt-mediated prosurvival signaling in human breast cancer cells. Int J Cancer 2009; 125(4): 961-7.
[http://dx.doi.org/10.1002/ijc.24419] [PMID: 19384950]
[23]
Chen Y, Tang YM, Yu SL, et al. Advances in the pharmacological activities and mechanisms of diosgenin. Chin J Nat Med 2015; 13(8): 578-87.
[http://dx.doi.org/10.1016/S1875-5364(15)30053-4] [PMID: 26253490]
[24]
Li F, Fernandez PP, Rajendran P, Hui KM, Sethi G. Diosgenin, a steroidal saponin, inhibits STAT3 signaling pathway leading to suppression of proliferation and chemosensitization of human hepatocellular carcinoma cells. Cancer Lett 2010; 292(2): 197-207.
[http://dx.doi.org/10.1016/j.canlet.2009.12.003] [PMID: 20053498]
[25]
Lepage C, Léger DY, Bertrand J, Martin F, Beneytout JL, Liagre B. Diosgenin induces death receptor-5 through activation of p38 pathway and promotes TRAIL-induced apoptosis in colon cancer cells. Cancer Lett 2011; 301(2): 193-202.
[http://dx.doi.org/10.1016/j.canlet.2010.12.003] [PMID: 21195543]
[26]
Song JX, Ma L, Kou JP, Yu BY. Diosgenin reduces leukocytes adhesion and migration linked with inhibition of intercellular adhesion molecule-1 expres-sion and NF-kB p65 activation in endothelial cells. Chin J Nat Med 2012; 10(2): 142-9.
[http://dx.doi.org/10.3724/SP.J.1009.2012.00142]
[27]
Choi KW, Park HJ, Jung DH, et al. Inhibition of TNF-α-induced adhesion molecule expression by diosgenin in mouse vascular smooth muscle cells via downregulation of the MAPK, Akt and NF-κB signaling pathways. Vascul Pharmacol 2010; 53(5-6): 273-80.
[http://dx.doi.org/10.1016/j.vph.2010.09.007] [PMID: 20932938]
[28]
Raju J, Mehta R. Cancer chemopreventive and therapeutic effects of diosgenin, a food saponin. Nutr Cancer 2009; 61(1): 27-35.
[http://dx.doi.org/10.1080/01635580802357352] [PMID: 19116873]
[29]
Price KR, Johnson IT, Fenwick GR, Malinow MR. The chemistry and biological significance of saponins in foods and feedingstuffs. CRC Crit Rev Food Sci Nutr 1987; 26(1): 27-135.
[http://dx.doi.org/10.1080/10408398709527461] [PMID: 3308321]
[30]
Fenwick GR, Price KR, Tsukamoto C, Okubo K. Saponins. In:Toxic Substances in Crop Plants. Cambridge: The Royal Society of Chemistry 1991; pp. 285-327.
[31]
Raju J, Rao CV. Diosgenin, a steroid saponin constituent of yams and fenugreek: Emerging evidence for applications in medicine. In:Bioactive compounds in phytomedicine. Intech Open 2012; pp. 125-42.
[32]
Deshpande HA, Bhalsing SR. Plant derived novel biomedicinal: diosgenin. Int J Pharmacogn Phytochem Res 2014; 6(4): 780-4.
[33]
Alice CB, Vargas VMF, Silva GAAB, et al. Screening of plants used in South Brazilian folk medicine. J Ethnopharmacol 1991; 35(2): 165-71.
[http://dx.doi.org/10.1016/0378-8741(91)90069-P] [PMID: 1809823]
[34]
Liu J, Henkel T. Traditional Chinese Medicine (TCM): are polyphenols and saponins the key ingredients triggering biological activities? Curr Med Chem 2002; 9(15): 1483-5.
[http://dx.doi.org/10.2174/0929867023369709] [PMID: 12173978]
[35]
Tong QY, He Y, Zhao QB, Qing Y, Huang W, Wu XH. Cytotoxicity and apoptosis-inducing effect of steroidal saponins from Dioscorea zingiberensis Wright against cancer cells. Steroids 2012; 77(12): 1219-27.
[http://dx.doi.org/10.1016/j.steroids.2012.04.019] [PMID: 22575181]
[36]
Salvador JAR, Carvalho JFS, Neves MAC, et al. Anticancer steroids: linking natural and semi-synthetic compounds. Nat Prod Rep 2013; 30(2): 324-74.
[http://dx.doi.org/10.1039/C2NP20082A] [PMID: 23151898]
[37]
Trouillas P, Corbière C, Liagre B, Duroux JL, Beneytout JL. Structure–function relationship for saponin effects on cell cycle arrest and apoptosis in the human 1547 osteosarcoma cells: a molecular modelling approach of natural molecules structurally close to diosgenin. Bioorg Med Chem 2005; 13(4): 1141-9.
[http://dx.doi.org/10.1016/j.bmc.2004.11.031] [PMID: 15670922]
[38]
Brahmachari G, Ed. Chemistry and Pharmacology of Naturally occurring Bioactive Compounds. Boca Raton: Taylor & Francis Group 2013.
[http://dx.doi.org/10.1201/b13867]
[39]
Deshpande HA, Bhalsing SR. Recent advances in the phytochemistry of some medicinally important Cassia species: A review. Int J Pharm Med Biol Sci 2013; 2(3): 60-78.
[40]
Sautour M, Mitaine-Offer A-C, Miyamoto T, Dongmo A, Lacaille-Dubois M-A. Antifungal steroid saponins from Dioscorea cayenensis. Planta Med 2004; 70(1): 90-2.
[http://dx.doi.org/10.1055/s-2004-815467] [PMID: 14765305]
[41]
Mirunalini S. Novel effects of diosgenin: A Plant derived steroid; A review. Pharmacology online Newsletter 2011; 1: 726-36.
[42]
Kambaska KB, Sahoo S, Prusti A. Biochemical quantification of diosgenin and ascorbic acid from the tubers of different dioscorea species found in Orissa. Libyan Agric Res Cen J Intl 2010; 1(2): 123-7.
[43]
Punyarani K, Sharma JG. Micropropagation of Costus speciosus (Koen.) Sm. using nodal segment culture. Not Sci Biol 2010; 2(1): 58-62.
[http://dx.doi.org/10.15835/nsb213552]
[44]
Singh I, Kumar GY, Vimala Y. Detection and isolation of diosgenin from Costus Speciosus callus raised from non-germinal seeds. Int J Chem and Life Sciences 2010; 2(10): 1240-2.
[45]
Deshpande HA, Bhalsing SR. Isolation and characterization of diosgenin from in vitro cultured tissues of Helicteres isora L. Physiol Mol Biol Plants 2014; 20(1): 89-94.
[http://dx.doi.org/10.1007/s12298-013-0205-3] [PMID: 24554842]
[46]
Kumar V, Desai D, Shriram V. Hairy root induction in Helicteres isora L. and production of diosgenin in hairy roots. Nat Prod Bioprospect 2014; 4(2): 107-12.
[http://dx.doi.org/10.1007/s13659-014-0011-9] [PMID: 24859054]
[47]
Cho J, Choi H, Lee J, Kim MS, Sohn HY, Lee DG. The antifungal activity and membrane-disruptive action of dioscin extracted from Dioscorea nipponica. Biochim Biophys Acta Biomembr 2013; 1828(3): 1153-8.
[http://dx.doi.org/10.1016/j.bbamem.2012.12.010] [PMID: 23262192]
[48]
Li P, Mao Z, Lou J, et al. Enhancement of diosgenin production in Dioscorea zingiberensis cell cultures by oligosaccharides from its endophytic fungus Fusarium oxysporum Dzf17. Molecules 2011; 16(12): 10631-44.
[http://dx.doi.org/10.3390/molecules161210631] [PMID: 22183887]
[49]
Li J, Liang Q, Li C, Liu M, Zhang Y. Comparative transcriptome analysis identifies putative genes involved in dioscin biosynthesis in Dioscorea zingiberensis. Molecules 2018; 23(2): 454-66.
[http://dx.doi.org/10.3390/molecules23020454] [PMID: 29463020]
[50]
De D, De B. Elicitation of diosgenin production in Dioscorea floribunda by ethylene-generating agent. Fitoterapia 2005; 76(2): 153-6.
[http://dx.doi.org/10.1016/j.fitote.2004.11.008] [PMID: 15752624]
[51]
Mulabagal V, Tsay HS. Plant cell cultures an alternative and efficient source for the production of biologically important secondary metabolites. Int J Appl Sci Eng 2004; 2(1): 29-48.
[52]
a) Das S, Dutta Choudhury M, Mazumdar PB. Micropropagation of Dioscorea alata L. through nodal segments. Afr J Biotechnol 2013; 12(47): 6611-7.
[http://dx.doi.org/10.5897/AJB2013.12191];
b) Wu ZG, Jiang W, Wei Y, Tao YH. New variety breeding of Dioscorea alata, cultivar. Zhongguo Zhongyao Zazhi 2015; 40(9): 1705-9.
[PMID: 26323133]
[53]
Kadota M, Niimi Y. Improvement of micropropagation of Japanese yam using liquid and gelled medium culture. Sci Hortic 2004; 102(4): 461-6.
[http://dx.doi.org/10.1016/j.scienta.2004.06.004]
[54]
Narula A, Kumar S, Srivastava PS. Genetic fidelity of in vitro regenerants, encapsulation of shoot tips and high diosgenin content in Dioscorea bulbifera L., a potential alternative source of diosgenin. Biotechnol Lett 2007; 29(4): 623-9.
[http://dx.doi.org/10.1007/s10529-006-9276-3] [PMID: 17318334]
[55]
Khatodia S, Biswas K, Bhatotia K. Induction and establishment of hairy root culture of Solanum xanthocarpum using Agrobacterium rhizogenes. J Pharm Biomed Sci 2013; 1: 59-63.
[56]
Solouki M, Hoshyar H, Ramroudi M, Tavassoli A. Comparison and evaluation of steroid alkaloid solasodine on in vivo and in vitro cultures of Solanum surattense Burm L. Afr J Microbiol Res 2011; 5(22): 3810-4.
[57]
Ashwani K. Improvement of fenugreek through breeding approaches and in vitro applications Am J Social issues and Humanities 2014; 3(4): 120-7.
[58]
Binesh A, Gnanam R. Diosgenin Production from Callus, Suspension and Hairy Root Cultures of Trigonella foenum-graecum. Adv Bio Tech 2009; 9: 33-40.
[59]
Rezaeian S. Assessment of Diosgenin production by Trigonella foenum – graecum L. in vitro conditions. Am J Plant Physiol 2011; 6(5): 261-8.
[http://dx.doi.org/10.3923/ajpp.2011.261.268]
[60]
Nikam TD, Ebrahimi MA, Patil VA. Embryogenic callus culture of Tribulus terrestris L. a potential source of harmaline, harmine and diosgenin. Plant Biotechnol Rep 2009; 3(3): 243-50.
[http://dx.doi.org/10.1007/s11816-009-0096-5]
[61]
Bhutani KK, Paul AT, Fayad W, Linder S. Apoptosis inducing activity of steroidal constituents from Solanum xanthocarpum and Asparagus racemosus. Phytomedicine 2010; 17(10): 789-93.
[http://dx.doi.org/10.1016/j.phymed.2010.01.017] [PMID: 20176464]
[62]
Lin RC, Lacaille-Dubois MA, Hanquet B, Correia M, Chauffert B. New diosgenin glycosides from Costus afer. J Nat Prod 1997; 60(11): 1165-9.
[http://dx.doi.org/10.1021/np9702190]
[63]
Prawat U, Tuntiwachwuttikul P, Taylor WC. Steroidal saponins of Costus lacerus. Sci Asia 1989; 15(2): 139-47.
[http://dx.doi.org/10.2306/scienceasia1513-1874.1989.15.139]
[64]
Asha KI, Nair GM. Screening of Dioscorea species for diosgenin from southern Western Ghats of India. Indian J Plant Genet Resour 2005; 18(2): 227-30.
[65]
Dong M, Feng X, Wang B, Wu L, Ikejima T. Two novel furostanol saponins from the rhizomes of Dioscorea panthaica Prain et Burkill and their cytotoxic activity. Tetrahedron 2001; 57(3): 501-6.
[http://dx.doi.org/10.1016/S0040-4020(00)01024-3]
[66]
Zhang Y, Jin L, Liu J, et al. Effect and mechanism of dioscin from Dioscorea spongiosa on uric acid excretion in animal model of hyperuricemia. J Ethnopharmacol 2018; 214: 29-36.
[http://dx.doi.org/10.1016/j.jep.2017.12.004] [PMID: 29233733]
[67]
Ali Z, Smillie TJ, Khan IA. Two spirostan steroid glycoside fatty esters from Dioscorea cayenensis Nat Prod Commun 2013; 8(3): 323-6. 1934578X1300800.
[http://dx.doi.org/10.1177/1934578X1300800311] [PMID: 23678801]
[68]
Su J, Wei Y, Liu M, et al. Anti-hyperuricemic and nephroprotective effects of Rhizoma Dioscoreae septemlobae extracts and its main component dioscin via regulation of mOAT1, mURAT1 and mOCT2 in hypertensive mice. Arch Pharm Res 2014; 37(10): 1336-44.
[http://dx.doi.org/10.1007/s12272-014-0413-6] [PMID: 24866061]
[69]
Kwon YK, Jie EY, Sartie A, et al. Rapid metabolic discrimination and prediction of dioscin content from African yam tubers using Fourier transform-infrared spectroscopy combined with multivariate analysis. Food Chem 2015; 166: 389-96.
[http://dx.doi.org/10.1016/j.foodchem.2014.06.035] [PMID: 25053072]
[70]
Pan CH, Tsai CH, Liu FC, et al. Influence of different particle processing on hypocholesterolemic and antiatherogenic activities of yam (Dioscorea pseudojaponica) in cholesterol-fed rabbit model. J Sci Food Agric 2013; 93(6): 1278-83.
[http://dx.doi.org/10.1002/jsfa.5882] [PMID: 23400896]
[71]
Lee HY, Jung DY, Ha H, Son K-H, Jeon S-J, Kim C. Induction of growth hormone release by dioscin from Dioscorea batatas DECNE. J Biochem Mol Biol 2007; 40(6): 1016-20.
[PMID: 18047799]
[72]
Yang SL, Ma YH, Liu XK. Steroidal constituents from Dioscorea parviflora. Yao Xue Xue Bao 2005; 40(2): 145-9.
[PMID: 15875671]
[73]
Liu HW, Hu K, Zhao QC, Cui CB, Kobayashi H, Yao XS. Bioactive saponins from Dioscorea futschauensis. Pharmazie 2002; 57(8): 570-2.
[PMID: 12227201]
[74]
Lee HJ, Park JS, Yoon YP, et al. Dioscin and methylprotodioscin isolated from the root of Asparagus cochinchinensis suppressed the gene expression and production of airway MUC5AC mucin induced by phorbol ester and growth factor. Phytomedicine 2015; 22(5): 568-72.
[http://dx.doi.org/10.1016/j.phymed.2015.03.009] [PMID: 25981923]
[75]
Zhu Y-H, Zhao M, Ren L, Tian D, Dou F, Wang JX. Studies on the chemical constituents from the flowers of Ophiopogon japonicus. Zhong Yao Cai 2011; 34(5): 720-3.
[PMID: 21954559]
[76]
Gao L-L, Li F-R, Jiao P, Yao ST, Sang H, Si Y-H. Apoptosis of human ovarian cancer cells induced by Paris Chinensis dioscin via a Ca(2+)-mediated mitochondrion pathway. Asian Pac J Cancer Prev 2011; 12(5): 1361-6.
[PMID: 21875297]
[77]
Xiao XH, Yuan ZQ, Li GK. Separation and purification of steroidal saponins from Paris polyphylla by microwave-assisted extraction coupled with countercurrent chromatography using evaporative light scattering detection. J Sep Sci 2014; 37(6): 635-41.
[http://dx.doi.org/10.1002/jssc.201301341] [PMID: 24772456]
[78]
Zhang YS, Ma YL, Thakur K, et al. Molecular mechanism and inhibitory targets of dioscin in HepG2 cells. Food Chem Toxicol 2018; 120: 143-54.
[http://dx.doi.org/10.1016/j.fct.2018.07.016] [PMID: 29990575]
[79]
Ivanova A, Mikhova B, Klaiber I, Dinchev D, Kostova I. Steroidal saponins from Smilax excelsa rhizomes. Nat Prod Res 2009; 23(10): 916-24.
[http://dx.doi.org/10.1080/14786410802624827] [PMID: 19521905]
[80]
Ju Y, Jia ZJ. Steroidal saponins from the rhizomes of Smilax menispermoidea. Phytochemistry 1992; 31(4): 1349-51.
[http://dx.doi.org/10.1016/0031-9422(92)80288-P] [PMID: 1368051]
[81]
Gao X, Sun W, Fu Q, Niu X. Rapid identification of steroidal saponins in Trillium tschonoskii Maxim. by ultra performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Phytochem Anal 2015; 26(4): 269-78.
[http://dx.doi.org/10.1002/pca.2560] [PMID: 25808861]
[82]
Manase MJ, Mitaine-Offer AC, Pertuit D, et al. Solanum incanum and S. heteracanthum as sources of biologically active steroid glycosides: Confirmation of their synonymy. Fitoterapia 2012; 83(6): 1115-9.
[http://dx.doi.org/10.1016/j.fitote.2012.04.024] [PMID: 22579841]
[83]
Nishina A, Ebina K, Ukiya M, et al. Dioscin derived from Solanum melongena L. “Usukawamarunasu” attenuates alpha-MSH-induced melanogenesis in B16 murine melanoma cells via down regulation of phospho-CREB and MITF. J Food Sci 2015; 80(10): H2354-9.
[http://dx.doi.org/10.1111/1750-3841.13068] [PMID: 26352003]
[84]
Hao LJ, Wang S, Zhu JJ, Wang ZM, Wei SH. Chemical constituents from Solanum rostratum. Zhongguo Zhongyao Zazhi 2014; 39(11): 2034-8.
[PMID: 25272837]
[85]
Yoshikawa M, Xu F, Morikawa T, et al. Medicinal flowers. XII.(1)) New spirostane-type steroid saponins with antidiabetogenic activity from Borassus flabellifer. Chem Pharm Bull 2007; 55(2): 308-16.
[http://dx.doi.org/10.1248/cpb.55.308] [PMID: 17268107]
[86]
Zhang Y, Li HZ, Zhang YJ, et al. Atropurosides A–G, new steroidal saponins from Smilacina atropurpurea. Steroids 2006; 71(8): 712-9.
[http://dx.doi.org/10.1016/j.steroids.2006.04.005] [PMID: 16766007]
[87]
Chaturvedi HC, Jain M, Kidwai NR. Cloning of medicinal plants through tissue culture-a review. Indian J Exp Biol 2007; 45(11): 937-48.
[PMID: 18072537]
[88]
Li X, Ma JZ, Shi YD. Research progress and prospects of dioscorea and diosgenin. Linchan Huaxue Yu Gongye 2010; 30(2): 107-12.
[89]
Cayen MN, Ferdinandi ES, Greselin E, Dvornik D. Studies on the disposition of diosgenin in rats, dogs, monkeys and man. Atherosclerosis 1979; 33(1): 71-87.
[http://dx.doi.org/10.1016/0021-9150(79)90199-0] [PMID: 111685]
[90]
Miles CO, Wilkins AL, Erasmus GL, Kellerman TS. Photosensitivity in South Africa. VIII. Ovine metabolism of Tribulus terrestris saponins during experimentally induced geeldikkop. Onderstepoort J Vet Res 1994; 61(4): 351-9.
[PMID: 7501366]
[91]
Wilkins AL, Miles CO, Smith BL, Meagher LP, Ede R. GC/MS method for the analysis of plant and animal samples associated with ovine photosensitization. In: Poisonous Plants of the world: Agriculture, Phytochemical and Ecological Aspects. Wallingford: CAB International 1994; pp. 263-8.
[92]
Zhang Y, Tang L, An X, Fu E, Ma C. Modification of cellulase and its application to extraction of diosgenin from Dioscorea zingiberensis C.H. Wright. Biochem Eng J 2009; 47(1-3): 80-6.
[http://dx.doi.org/10.1016/j.bej.2009.07.006]
[93]
Patel K, Gadewar M, Tahilyani V, Patel DK. A review on pharmacological and analytical aspects of diosgenin: a concise report. Nat Prod Bioprospect 2012; 2(2): 46-52.
[http://dx.doi.org/10.1007/s13659-012-0014-3]
[94]
Jesus M, Martins APJ, Gallardo E, Silvestre S. Diosgenin: Recent highlights on pharmacology and analytical methodology. J Anal Methods Chem 2016; 2016: 1-16.
[http://dx.doi.org/10.1155/2016/4156293] [PMID: 28116217]
[95]
Chiang CT, Way TD, Tsai SJ, Lin JK. Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation. FEBS Lett 2007; 581(30): 5735-42.
[http://dx.doi.org/10.1016/j.febslet.2007.11.021] [PMID: 18022396]
[96]
Balamurugan E, Manivannan J, Sivasubramanian J, Arunagiri P. Diosgenin prevents hepatic oxidative stress, lipid peroxidation and molecular alterations in chronic renal failure rats. Int J Nutr Pharmacol Neurol Dis 2013; 3(3): 289-94.
[http://dx.doi.org/10.4103/2231-0738.114870]
[97]
Roghani-Dehkordi F, Roghani M, Baluchnejadmojarad T. Diosgenin mitigates streptozotocin diabetes-induced vascular dysfunction of the rat aorta: the involved mechanisms. J Cardiovasc Pharmacol 2015; 66(6): 584-92.
[http://dx.doi.org/10.1097/FJC.0000000000000308] [PMID: 26309100]
[98]
Kalailingam P, Kannaian B, Tamilmani E, Kaliaperumal R. Efficacy of natural diosgenin on cardiovascular risk, insulin secretion, and beta cells in streptozotocin (STZ)-induced diabetic rats. Phytomedicine 2014; 21(10): 1154-61.
[http://dx.doi.org/10.1016/j.phymed.2014.04.005] [PMID: 24889525]
[99]
Huang B, Du D, Zhang R, et al. Synthesis, characterization and biological studies of diosgenyl analogues. Bioorg Med Chem Lett 2012; 22(24): 7330-4.
[http://dx.doi.org/10.1016/j.bmcl.2012.10.086] [PMID: 23153797]
[100]
Alcantara EH, Shin MY, Sohn HY, et al. Diosgenin stimulates osteogenic activity by increasing bone matrix protein synthesis and bone-specific transcription factor Runx2 in osteoblastic MC3T3-E1 cells. J Nutr Biochem 2011; 22(11): 1055-63.
[http://dx.doi.org/10.1016/j.jnutbio.2010.09.003] [PMID: 21292464]
[101]
Attele AS, Wu JA, Yuan CS. Ginseng pharmacology. Biochem Pharmacol 1999; 58(11): 1685-93.
[http://dx.doi.org/10.1016/S0006-2952(99)00212-9] [PMID: 10571242]
[102]
Raju J, Patlolla JMR, Swamy MV, Rao CV. Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells. Cancer Epidemiol Biomarkers Prev 2004; 13(8): 1392-8.
[http://dx.doi.org/10.1158/1055-9965.1392.13.8] [PMID: 15298963]
[103]
Sethi G, Shanmugam M, Warrier S, et al. Proapoptotic and anti-cancer properties of diosgenin: a comprehensive and critical review. Nutrients 2018; 10(5): 645.
[http://dx.doi.org/10.3390/nu10050645] [PMID: 29783752]
[104]
He Z, Chen H, Li G, et al. Diosgenin inhibits the migration of human breast cancer MDA-MB-231 cells by suppressing Vav2 activity. Phytomedicine 2014; 21(6): 871-6.
[http://dx.doi.org/10.1016/j.phymed.2014.02.002] [PMID: 24656238]
[105]
Razumilava N, Gores GJ. Cholangiocarcinoma. Lancet 2014; 383(9935): 2168-79.
[http://dx.doi.org/10.1016/S0140-6736(13)61903-0] [PMID: 24581682]
[106]
Mao XM, Zhou P, Li SY, et al. Diosgenin suppresses cholangiocarcinoma cells via inducing cell cycle arrest and mitochondria-mediated apoptosis. OncoTargets Ther 2019; 12: 9093-104.
[http://dx.doi.org/10.2147/OTT.S226261] [PMID: 31806994]
[107]
Wang Y, Yamaguchi Y, Watanabe H, Ohtsubo K, Wakabayashi T, Sawabu N. Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K- ras mutation. J Gastroenterol 2002; 37(10): 831-9.
[http://dx.doi.org/10.1007/s005350200137] [PMID: 12424567]
[108]
Furubo S, Harada K, Shimonishi T, Katayanagi K, Tsui W, Nakanuma Y. Protein expression and genetic alterations of p53 and ras in intrahepatic cholangiocarcinoma. Histopathology 1999; 35(3): 230-40.
[http://dx.doi.org/10.1046/j.1365-2559.1999.00705.x] [PMID: 10469215]
[109]
Wang L, Zhang J, Wan L, Zhou X, Wang Z, Wei W. Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther 2015; 151: 141-51.
[http://dx.doi.org/10.1016/j.pharmthera.2015.04.002] [PMID: 25850036]
[110]
Kim Y, Choi JW, Lee JH, Kim YS. MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol 2014; 33(5): 517-23.
[http://dx.doi.org/10.1097/PGP.0000000000000082] [PMID: 25083970]
[111]
Moura IMB, Delgado ML, Silva PMA, et al. High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma. J Oral Pathol Med 2014; 43(3): 225-31.
[http://dx.doi.org/10.1111/jop.12115] [PMID: 24044615]
[112]
Wu W, Hu K, Wang D, et al. CDC20 overexpression predicts a poor prognosis for patients with colorectal cancer. J Transl Med 2013; 11(1): 142.
[http://dx.doi.org/10.1186/1479-5876-11-142] [PMID: 23758705]
[113]
Gayyed MF, El-Maqsoud NMRA, Tawfiek ER, El Gelany SAA, Rahman MFA. A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: its correlation with tumor grade and stage. Tumour Biol 2016; 37(1): 749-62.
[http://dx.doi.org/10.1007/s13277-015-3808-1] [PMID: 26245990]
[114]
Li J, Gao JZ, Du JL, Huang ZX, Wei LX. Increased CDC20 expression is associated with development and progression of Hepatocellular carcinoma. Int J Oncol 2014; 45(4): 1547-55.
[http://dx.doi.org/10.3892/ijo.2014.2559] [PMID: 25069850]
[115]
Ding ZY, Wu HR, Zhang JM, Huang G-R, Ji D-D. Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J Clin Exp Pathol 2014; 7(2): 722-7.
[PMID: 24551295]
[116]
Choi JW, Kim Y, Lee JH, Kim YS. High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer. Virchows Arch 2013; 463(5): 681-7.
[http://dx.doi.org/10.1007/s00428-013-1473-6] [PMID: 23995871]
[117]
Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M. Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients. J Surg Oncol 2012; 106(4): 423-30.
[http://dx.doi.org/10.1002/jso.23109] [PMID: 22488197]
[118]
Chang DZ, Ma Y, Ji B, et al. Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol 2012; 5(1): 15. http://www.jhoonline.org/content/5/1/15
[http://dx.doi.org/10.1186/1756-8722-5-15] [PMID: 22475564]
[119]
Corbiere C, Liagre B, Bianchi A, et al. Different contribution of apoptosis to the antiproliferative effects of diosgenin and other plant steroids, hecogenin and tigogenin, on human 1547 osteosarcoma cells. Int J Oncol 2003; 22(4): 899-905.
[http://dx.doi.org/10.3892/ijo.22.4.899] [PMID: 12632085]
[120]
Li YW, Qi J, Zhang YY, et al. Novel cytotoxic steroidal glycosides from the roots of Liriope muscari. Chin J Nat Med 2015; 13(6): 461-6.
[http://dx.doi.org/10.1016/S1875-5364(15)30040-6] [PMID: 26073343]
[121]
Zheng L, Zhou Y, Zhang JY, et al. Two new steroidal saponins from the rhizomes of Dioscorea zingiberensis. Chin J Nat Med 2014; 12(2): 142-7.
[http://dx.doi.org/10.1016/S1875-5364(14)60023-6] [PMID: 24636066]
[122]
Jan TR, Wey SP, Kuan CC, Liao MH, Wu HY. Diosgenin, a steroidal sapogenin, enhances antigen-specific IgG2a and interferon-gamma expression in ovalbumin-sensitized BALB/c mice. Planta Med 2007; 73(5): 421-6.
[http://dx.doi.org/10.1055/s-2007-967169] [PMID: 17566144]
[123]
Dong M, Meng Z, Kuerban K, et al. Diosgenin promotes antitumor immunity and PD-1 antibody efficacy against melanoma by regulating intestinal microbiota. Cell Death Dis 2018; 9(10): 1039.
[http://dx.doi.org/10.1038/s41419-018-1099-3] [PMID: 30305604]
[124]
Yang L, Ren S, Xu F, Ma Z, Liu X, Wang L. Recent advances in the pharmacological activities of dioscin. BioMed Res Int 2019.
[http://dx.doi.org/10.1155/2019/5763602]
[125]
Zhao X, Tao X, Xu L, et al. Dioscin induces apoptosis in human cervical carcinoma HeLa and SiHa cells through ROS mediated DNA damage and the mitochondrial signaling pathway. Molecules 2016; 21(6): 730.
[http://dx.doi.org/10.3390/molecules21060730] [PMID: 27271587]
[126]
Chen J, Li H, Zhang X, Xiong C, Ruan J. Dioscin-induced apoptosis of human LNCaP prostate carcinoma cells through activation of caspase-3 and modulation of Bcl-2 protein family. J Huazhong Univ Sci Technolog Med Sci 2014; 34(1): 125-30.
[http://dx.doi.org/10.1007/s11596-014-1243-y] [PMID: 24496691]
[127]
Zhao X, Xu L, Zheng L, et al. Potent effects of dioscin against gastric cancer in vitro and in vivo. Phytomedicine 2016; 23(3): 274-82.
[http://dx.doi.org/10.1016/j.phymed.2016.01.012] [PMID: 26969381]
[128]
Lv L, Zheng L, Dong D, et al. Dioscin, a natural steroid saponin, induces apoptosis and DNA damage through reactive oxygen species: A potential new drug for treatment of glioblastoma multiforme. Food Chem Toxicol 2013; 59: 657-69.
[http://dx.doi.org/10.1016/j.fct.2013.07.012] [PMID: 23871826]
[129]
Zhiyu W, Yue C, Neng W, et al. Dioscin induces cancer cell apoptosis through elevated oxidative stress mediated by downregulation of peroxiredoxins. Cancer Biol Ther 2012; 13(3): 138-47.
[http://dx.doi.org/10.4161/cbt.13.3.18693] [PMID: 22231406]
[130]
Song X, Wang Z, Liang H, et al. Dioscin induces gallbladder cancer apoptosis by inhibiting ROS-mediated PI3K/AKT Signalling. Int J Biol Sci 2017; 13(6): 782-93.
[http://dx.doi.org/10.7150/ijbs.18732] [PMID: 28656003]
[131]
Wang Y, He QY, Chiu JF. Dioscin induced activation of p38 MAPK and JNK via mitochondrial pathway in HL-60 cell line. Eur J Pharmacol 2014; 735: 52-8.
[http://dx.doi.org/10.1016/j.ejphar.2014.04.018] [PMID: 24755146]
[132]
Si L, Zheng L, Xu L, et al. Dioscin suppresses human laryngeal cancer cells growth via induction of cell-cycle arrest and MAPK-mediated mitochondrial-derived apoptosis and inhibition of tumor invasion. Eur J Pharmacol 2016; 774: 105-17.
[http://dx.doi.org/10.1016/j.ejphar.2016.02.009] [PMID: 26849940]
[133]
Kim EA, Jang JH, Lee YH, et al. Dioscin induces caspase-independent apoptosis through activation of apoptosis-inducing factor in breast cancer cells. Apoptosis 2014; 19(7): 1165-75.
[http://dx.doi.org/10.1007/s10495-014-0994-z] [PMID: 24771279]
[134]
Chen H, Xu L, Yin L, et al. iTRAQ-based proteomic analysis of dioscin on human HCT-116 colon cancer cells. Proteomics 2014; 14(1): 51-73.
[http://dx.doi.org/10.1002/pmic.201300101] [PMID: 24420967]
[135]
Zhou Q, Song W, Xiao W. Dioscin induces demethylation of DAPK-1 and RASSF-1alpha genes via the antioxidant capacity, resulting in apoptosis of bladder cancer T24 cells. EXCLI J 2017; 16: 101-12.
[PMID: 28435431]
[136]
Kim YS, Kim EA, Park KG, et al. Dioscin sensitizes cells to TRAIL-induced apoptosis through downregulation of c-FLIP and Bcl-2. Oncol Rep 2012; 28(5): 1910-6.
[http://dx.doi.org/10.3892/or.2012.1962] [PMID: 22895655]
[137]
Gao LL, Li F-R, Jiao P, et al. Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells. World J Gastroenterol 2011; 17(39): 4389-95.
[http://dx.doi.org/10.3748/wjg.v17.i39.4389] [PMID: 22110264]
[138]
Hsieh MJ, Tsai TL, Hsieh YS, Wang CJ, Chiou HL. Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines. Arch Toxicol 2013; 87(11): 1927-37.
[http://dx.doi.org/10.1007/s00204-013-1047-z] [PMID: 23552851]
[139]
Wang C, Huo X, Wang L, et al. Dioscin strengthens the efficiency of adriamycin in MCF-7 and MCF-7/ADR cells through autophagy induction: More than just down-regulation of MDR1. Sci Rep 2016; 6(1): 28403.
[http://dx.doi.org/10.1038/srep28403] [PMID: 27329817]
[140]
Chan SH, Liang PH, Guh JH. An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia. Naunyn Schmiedebergs Arch Pharmacol 2018; 391(6): 587-602.
[http://dx.doi.org/10.1007/s00210-018-1484-6] [PMID: 29594316]
[141]
Ganesan N, Arockiam AJV. Diosgenin decrease proliferation of human lung cancer cells by promoting cholesterol efflux via up-regulation of LXR-alpha and its target ABCA1 expression. Asian J Pharm Pharmacol 2019; 5(4): 804-9.
[http://dx.doi.org/10.31024/ajpp.2019.5.4.22]
[142]
Mohammad RY, Somayyeh G, Gholamreza H, Majid M, Yousef R. Diosgenin inhibits hTERT gene expression in the A549 lung cancer cell line. Asian Pac J Cancer Prev 2013; 14(11): 6945-8.
[http://dx.doi.org/10.7314/APJCP.2013.14.11.6945] [PMID: 24377630]
[143]
Kim SY, Lim EJ, Yoon YS, et al. Liver X receptor and STAT1 cooperate downstream of Gas6/Mer to induce anti-inflammatory arginase 2 expression in macrophages. Sci Rep 2016; 6(1): 29673.
[http://dx.doi.org/10.1038/srep29673] [PMID: 27406916]
[144]
van der Waal I. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 2009; 45(4-5): 317-23.
[http://dx.doi.org/10.1016/j.oraloncology.2008.05.016] [PMID: 18674954]
[145]
Wang X, Sun C, He S, et al. Apoptotic effects of diosgeninlactoside on oral squamous carcinoma cells in vitro and in vivo. Biol Pharm Bull 2014; 37(9): 1450-9.
[http://dx.doi.org/10.1248/bpb.b14-00122] [PMID: 25177028]
[146]
Li Y, Wang X, Cheng S, et al. Diosgenin induces G2/M cell cycle arrest and apoptosis in human hepatocellular carcinoma cells. Oncol Rep 2015; 33(2): 693-8.
[http://dx.doi.org/10.3892/or.2014.3629] [PMID: 25434486]
[147]
Chen Z, Xu J, Wu Y, et al. Diosgenin inhibited the expression of TAZ in hepatocellular carcinoma. Biochem Biophys Res Commun 2018; 503(3): 1181-5.
[http://dx.doi.org/10.1016/j.bbrc.2018.07.022] [PMID: 30005871]
[148]
Dai Y, Miao Y, Wu W, et al. Ablation of Liver X receptors α and beta leads to spontaneous peripheral squamous cell lung cancer in mice. Proc Natl Acad Sci USA 2016; 113(27): 7614-9.
[http://dx.doi.org/10.1073/pnas.1607590113] [PMID: 27335465]
[149]
Wang L, Meng Q, Wang C, et al. Dioscin restores the activity of the anticancer agent adriamycin in multidrug-resistant human leukemia K562/adriamycin cells by down-regulating MDR1 via a mechanism involving NF-κB signaling inhibition. J Nat Prod 2013; 76(5): 909-14.
[http://dx.doi.org/10.1021/np400071c] [PMID: 23621869]
[150]
Benedetti G, Fredriksson L, Herpers B, Meerman J. TNF-alpha-mediated NF-kappa B survival signaling impairment by cisplatin enhances NK activation allowing synergistic apoptosis of renal proximal tubular cells. Biochem Pharmacol 2013; 85: 274-86.
[http://dx.doi.org/10.1016/j.bcp.2012.10.012] [PMID: 23103562]
[151]
Chang L, Kamata H, Solinas G, et al. The E3 ubiquitin ligaseitch couples JNK activation to TNF-alpha-induced cell death by inducing c-FLIP(L) turnover. Cell1 2006; 24: 601-13.
[152]
Sowmyalakshmi S, Ranga R, Gairola CG, Chendil D. Effect of diosgenin (Fenugreek) on breast cancer cells. Proc Am Assoc Cancer Res 2005; 46: 1382.
[153]
Michalak O, Krzeczyński P, Cieślak M, et al. Synthesis and anti–tumour, immunomodulating activity of diosgenin and tigogenin conjugates. J Steroid Biochem Mol Biol 2020; 198105573
[http://dx.doi.org/10.1016/j.jsbmb.2019.105573] [PMID: 32017993]
[154]
Chun J, Han L, Xu MY, Wang B, Cheng MS, Kim YS. The induction of apoptosis by a newly synthesized diosgenyl saponin through the suppression of estrogen receptor-α in MCF-7 human breast cancer cells. Arch Pharm Res 2014; 37(11): 1477-86.
[http://dx.doi.org/10.1007/s12272-013-0279-z] [PMID: 24263408]
[155]
Saarikangas J, Zhao H, Lappalainen P. Regulation of the actin cytoskeleton-plasma membrane interplay by phosphoinositides. Physiol Rev 2010; 90(1): 259-89.
[http://dx.doi.org/10.1152/physrev.00036.2009] [PMID: 20086078]
[156]
Raju J, Bird RP. Diosgenin, a naturally occurring furostanol saponin suppresses 3-hydroxy-3-methylglutaryl CoA reductase expression and induces apoptosis in HCT-116 human colon carcinoma cells. Cancer Lett 2007; 255(2): 194-204.
[http://dx.doi.org/10.1016/j.canlet.2007.04.011] [PMID: 17555873]
[157]
Manobharathi V, Mirunalini S. Pharmacological characteristics of a phytosteroidal food saponin: Diosgenin. Afr J Bio Sc 2020; 2(2): 77-87.
[158]
Miyoshi N, Nagasawa T, Mabuchi R, et al. Chemoprevention of azoxymethane/dextran sodium sulfate-induced mouse colon carcinogenesis by freeze-dried yam sanyaku and its constituent diosgenin. Cancer Prev Res 2011; 4(6): 924-34.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0279] [PMID: 21367960]
[159]
Tong Q, Qing Y, Wu Y, Hu X, Jiang L, Wu X. Dioscin inhibits colon tumor growth and tumor angiogenesis through regulating VEGFR2 and AKT/MAPK signaling pathways. Toxicol Appl Pharmacol 2014; 281(2): 166-73.
[http://dx.doi.org/10.1016/j.taap.2014.07.026] [PMID: 25111127]
[160]
Yi T, Cho SG, Yi Z, et al. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Cancer Ther 2008; 7(7): 1789-96.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0124] [PMID: 18644991]
[161]
Cargnello M, Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 2011; 75(1): 50-83.
[http://dx.doi.org/10.1128/MMBR.00031-10] [PMID: 21372320]
[162]
Rahmati-Yamchi M, Ghareghomi S, Haddadchi G, Milani M, Aghazadeh M, Daroushnejad H. Fenugreek extract diosgenin and pure diosgenin inhibit the hTERT gene expression in A549 lung cancer cell line. Mol Biol Rep 2014; 41(9): 6247-52.
[http://dx.doi.org/10.1007/s11033-014-3505-y] [PMID: 24973886]
[163]
Jiang S, Fan J, Wang Q, et al. Diosgenin induces ROS-dependent autophagy and cytotoxicity via mTOR signaling pathway in chronic myeloid leukemia cells. Phytomedicine 2016; 23(3): 243-52.
[http://dx.doi.org/10.1016/j.phymed.2016.01.010] [PMID: 26969378]
[164]
Jeyamohan S, Moorthy RK, Kannan MK, Arockiam AJV. Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer. Biotechnol Lett 2016; 38(8): 1251-60.
[http://dx.doi.org/10.1007/s10529-016-2102-7] [PMID: 27099069]
[165]
Chang HY, Kao MC, Way TD, Ho CT, Fu E. Diosgenin suppresses hepatocyte growth factor (HGF)-induced epithelial-mesenchymal transition by down-regulation of Mdm2 and vimentin. J Agric Food Chem 2011; 59(10): 5357-63.
[http://dx.doi.org/10.1021/jf200598w] [PMID: 21504235]
[166]
Liu MJ, Wang Z, Ju Y, Wong RNS, Wu QY. Diosgenin induces cell cycle arrest and apoptosis in human leukemia K562 cells with the disruption of Ca2+ homeostasis. Cancer Chemother Pharmacol 2005; 55(1): 79-90.
[http://dx.doi.org/10.1007/s00280-004-0849-3] [PMID: 15372201]
[167]
Hamid AA, Kaushal T, Ashraf R, et al. (22beta,25R)-3beta-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway. Steroids 2017; 119: 43-52.
[http://dx.doi.org/10.1016/j.steroids.2017.01.001] [PMID: 28143704]
[168]
Kang KB, Ryu J, Cho Y, Choi SZ, Son M, Sung SH. Combined application of UHPLC-QTOF/MS, HPLCELSD and 1H-NMR spectroscopy for quality assessment of DA9801, a standardised dioscorea extract. Phytochem Anal 2017; 28(3): 185-94.
[http://dx.doi.org/10.1002/pca.2659] [PMID: 27910174]
[169]
Liu Z, Zou W, Wang R, Zhou Z. The review and therapeutic effect analysis for ten-years clinical application of Di-ao-xin-xue-kang. Zhonghua Zhongyiyao Zazhi 2004; 19: 620-2.
[170]
Aumsuwan P, Khan SI, Khan IA, et al. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro. Arch Biochem Biophys 2016; 591: 98-110.
[http://dx.doi.org/10.1016/j.abb.2015.12.001] [PMID: 26682631]
[171]
Xu T, Zhang S, Zheng L, Yin L, Xu L, Peng J. A 90-day subchronic toxicological assessment of dioscin, a natural steroid saponin, in Sprague–Dawley rats. Food Chem Toxicol 2012; 50(5): 1279-87.
[http://dx.doi.org/10.1016/j.fct.2012.02.027] [PMID: 22386816]
[172]
Kaskiw MJ, Tassotto ML, Mok M, et al. Structural analogues of diosgenyl saponins: Synthesis and anticancer activity. Bioorg Med Chem 2009; 17(22): 7670-9.
[http://dx.doi.org/10.1016/j.bmc.2009.09.046] [PMID: 19819703]
[173]
Chen P, Wang P, Song N, Li M. Convergent synthesis and cytotoxic activities of 26-thio- and selenodioscin. Steroids 2013; 78(9): 959-66.
[http://dx.doi.org/10.1016/j.steroids.2013.05.018] [PMID: 23751199]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy