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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Mini-Review Article

Present and Future Prospects of the Anti-cancer Activities of Saikosaponins

Author(s): Li-Xia Xiao, Hui-Nian Zhou and Zuo-Yi Jiao*

Volume 23, Issue 1, 2023

Published on: 05 September, 2022

Page: [2 - 14] Pages: 13

DOI: 10.2174/1568009622666220806121008

Price: $65

Abstract

Since their discovery, saikosaponins (SSs) have been found to play an important role in treating a variety of cancers via diverse mechanisms of action. This review summarizes the current research status and prospects of the anti-cancer activities of SSs, providing novel insights into the limitations of current studies. In addition, it discusses whether SSs can be applied in immunotherapy and the possible mechanisms by which SSs may facilitate immunotherapy. The research is significant to understanding the anti-cancer potents of SSs in the development of SSs-based therapeutic strategies and clinical practice.

Keywords: Saikosaponin A, saikosaponin B, saikosaponin C, saikosaponin D, cancer, MDR.

Graphical Abstract
[1]
Yang, S.M.; Huang, C.; Li, X.F.; Yu, M.Z.; He, Y.; Li, J. miR-21 confers cisplatin resistance in gastric cancer cells by regulating PTEN. Toxicology, 2013, 306, 162-168.
[http://dx.doi.org/10.1016/j.tox.2013.02.014] [PMID: 23466500]
[2]
Panda, M.; Biswal, B.K. Cell signaling and cancer: A mechanistic insight into drug resistance. Mol. Biol. Rep., 2019, 46(5), 5645-5659.
[http://dx.doi.org/10.1007/s11033-019-04958-6] [PMID: 31280421]
[3]
Yang, F.; Dong, X.; Yin, X.; Wang, W.; You, L.; Ni, J. Radix bupleuri: A review of traditional uses, botany, phytochemistry, pharmacology, and toxicology. BioMed Res. Int., 2017, 2017, 7597596.
[http://dx.doi.org/10.1155/2017/7597596] [PMID: 28593176]
[4]
Cheng, T.; Ying, M. Antitumor effect of saikosaponin A on human neuroblastoma cells. BioMed Res. Int., 2021, 2021, 5845554.
[http://dx.doi.org/10.1155/2021/5845554] [PMID: 34513994]
[5]
Luo, J.; Wang, J.; Yang, J.; Huang, W.; Liu, J.; Tan, W.; Xin, H. Saikosaponin B1 and Saikosaponin D inhibit tumor growth in medullo-blastoma allograft mice via inhibiting the Hedgehog signaling pathway. J. Nat. Med., 2022, 76(3), 584-593.
[http://dx.doi.org/10.1007/s11418-022-01603-8] [PMID: 35171398]
[6]
Zhao, X.; Liu, J.; Ge, S.; Chen, C.; Li, S.; Wu, X.; Feng, X.; Wang, Y.; Cai, D.; Saikosaponin, A. Saikosaponin A inhibits breast cancer by regulating Th1/Th2 balance. Front. Pharmacol., 2019, 10, 624.
[http://dx.doi.org/10.3389/fphar.2019.00624] [PMID: 31214035]
[7]
Sun, K.; Du, Y.; Hou, Y.; Zhao, M.; Li, J.; Du, Y.; Zhang, L.; Chen, C.; Yang, H.; Yan, F.; Su, R. Saikosaponin D exhibits anti-leukemic activity by targeting FTO/m6A signaling. Theranostics, 2021, 11(12), 5831-5846.
[http://dx.doi.org/10.7150/thno.55574] [PMID: 33897884]
[8]
Zhang, C.Y.; Jiang, Z.M.; Ma, X.F.; Li, Y.; Liu, X.Z.; Li, L.L.; Wu, W.H.; Wang, T. Saikosaponin-d inhibits the hepatoma cells and en-hances chemosensitivity through SENP5-dependent inhibition of Gli1 SUMOylation under hypoxia. Front. Pharmacol., 2019, 10, 1039.
[http://dx.doi.org/10.3389/fphar.2019.01039] [PMID: 31616295]
[9]
Wu, S.; Chen, W.; Liu, K.; Ren, F.; Zheng, D.; Xu, F.; Wu, H. Saikosaponin D inhibits proliferation and induces apoptosis of non-small cell lung cancer cells by inhibiting the STAT3 pathway. J. Int. Med. Res., 2020, 48(9), 300060520937163.
[http://dx.doi.org/10.1177/0300060520937163] [PMID: 32962498]
[10]
Lai, M.; Ge, Y.; Chen, M.; Sun, S.; Chen, J.; Cheng, R.; Saikosaponin, D. Saikosaponin D inhibits proliferation and promotes apoptosis through activation of MKK4-JNK signaling pathway in pancreatic cancer cells. OncoTargets Ther., 2020, 13, 9465-9479.
[http://dx.doi.org/10.2147/OTT.S263322] [PMID: 33061432]
[11]
Hu, S.C.; Lai, Y.C.; Lin, C.L.; Tzeng, W.S.; Yen, F.L. Inclusion complex of saikosaponin-d with hydroxypropyl-β-cyclodextrin: Improved physicochemical properties and anti-skin cancer activity. Phytomedicine, 2019, 57, 174-182.
[http://dx.doi.org/10.1016/j.phymed.2018.11.012] [PMID: 30776588]
[12]
Zhao, L.; Li, J.; Sun, Z.B.; Sun, C.; Yu, Z.H.; Guo, X. Saikosaponin D inhibits proliferation of human osteosarcoma cells via the p53 signaling pathway. Exp. Ther. Med., 2019, 17(1), 488-494.
[http://dx.doi.org/10.3892/etm.2018.6969] [PMID: 30651826]
[13]
Cai, C.; Zhang, H.; Ou, Y.; Jiang, Y.; Zhong, D.; Qi, H.; Dang, Q. Saikosaponin-D suppresses cell growth in renal cell carcinoma through EGFR/p38 signaling pathway. Neoplasma, 2017, 64(4), 518-525.
[http://dx.doi.org/10.4149/neo_2017_405] [PMID: 28485157]
[14]
Li, Y.; Cai, T.; Zhang, W.; Zhu, W.; Lv, S. Effects of Saikosaponin D on apoptosis in human U87 glioblastoma cells. Mol. Med. Rep., 2017, 16(2), 1459-1464.
[http://dx.doi.org/10.3892/mmr.2017.6765] [PMID: 28627659]
[15]
Zhong, D.; Zhang, H.J.; Jiang, Y.D.; Wu, P.; Qi, H.; Cai, C.; Zheng, S.B.; Dang, Q. Saikosaponin-d: A potential chemotherapeutics in castration resistant prostate cancer by suppressing cancer metastases and cancer stem cell phenotypes. Biochem. Biophys. Res. Commun., 2016, 474(4), 722-729.
[http://dx.doi.org/10.1016/j.bbrc.2016.05.017] [PMID: 27155154]
[16]
Shin, J.E.; Kim, H.J.; Kim, K.R.; Lee, S.K.; Park, J.; Kim, H.; Park, K.K.; Chung, W.Y. Type I saikosaponins A and D inhibit osteoclastogenesis in bone marrow-derived macrophages and osteolytic activity of metastatic breast cancer cells. Evid. Based Complement. Alternat. Med., 2015, 2015, 582437.
[http://dx.doi.org/10.1155/2015/582437] [PMID: 25892999]
[17]
Liu, R.Y.; Li, J.P. Saikosaponin-d inhibits proliferation of human undifferentiated thyroid carcinoma cells through induction of apoptosis and cell cycle arrest. Eur. Rev. Med. Pharmacol. Sci., 2014, 18(17), 2435-2443.
[PMID: 25268087]
[18]
Ma, H.; Yokoyama, S.; Saiki, I.; Hayakawa, Y. Chemosensitizing effect of Saikosaponin B on B16F10 melanoma cells. Nutr. Cancer, 2017, 69(3), 505-511.
[http://dx.doi.org/10.1080/01635581.2017.1285407] [PMID: 28287317]
[19]
Tsai, Y.J.; Chen, I.L.; Horng, L.Y.; Wu, R.T. Induction of differentiation in rat C6 glioma cells with Saikosaponins. Phytother. Res., 2002, 16(2), 117-121.
[http://dx.doi.org/10.1002/ptr.752] [PMID: 11933111]
[20]
Du, J.; Song, D.; Cao, T.; Li, Y.; Liu, J.; Li, B.; Li, L. Saikosaponin-A induces apoptosis of cervical cancer through mitochondria- and endoplasmic reticulum stress-dependent pathway in vitro and in vivo: Involvement of PI3K/AKT signaling pathway. Cell Cycle, 2021, 20(21), 2221-2232.
[http://dx.doi.org/10.1080/15384101.2021.1974791] [PMID: 34520332]
[21]
Qi, X.; Fan, M.; Huang, N.; Zhang, X.; Liu, J.; Li, X.; Sun, R. Saikosaponin d contributed to cancer chemotherapy induced neutropenia therapy by promoting neutrophil differentiation via activation CBL-dependent ERK pathway. Pharmacol. Res., 2020, 160, 105149.
[http://dx.doi.org/10.1016/j.phrs.2020.105149] [PMID: 32822868]
[22]
Tian, Y.D.; Lin, S.; Yang, P.T.; Bai, M.H.; Jin, Y.Y.; Min, W.L.; Ma, H.B.; Wang, B.F. Saikosaponin-D increases the radiosensitivity of hepatoma cells by adjusting cell autophagy. J. Cancer, 2019, 10(20), 4947-4953.
[http://dx.doi.org/10.7150/jca.30286] [PMID: 31598167]
[23]
Tang, J.C.; Long, F.; Zhao, J.; Hang, J.; Ren, Y.G.; Chen, J.Y.; Mu, B. The effects and mechanisms by which saikosaponin-D enhances the sensitivity of human non-small cell lung cancer cells to Gefitinib. J. Cancer, 2019, 10(26), 6666-6672.
[http://dx.doi.org/10.7150/jca.30361] [PMID: 31777595]
[24]
Li, C.; Xue, H.G.; Feng, L.J.; Wang, M.L.; Wang, P.; Gai, X.D. The effect of saikosaponin D on doxorubicin pharmacokinetics and its MDR reversal in MCF-7/adr cell xenografts. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(19), 4437-4445.
[PMID: 29077148]
[25]
Foshan Aurora Biotechnology Co., Ltd.. A kind of preparation method of saikosaponin. China Patent No. CN201910436279 2019.
[26]
Shaanxi University of Chinese Medicine. A method for optimizing the ultrasonic extraction process of saikosaponin a test substance. China Patent No. CN201910025400 2019.
[27]
Foshan Aurora Biotechnology Co., Ltd.. A kind of saikosaponin extraction process. China Patent No. CN201811002124 2018.
[28]
Shanxi University of Chinese Medicine. A kind of extraction method of Saikosaponin A, C and D in Bupleurum medicinal material. China Patent No. CN201710867932 2018.
[29]
Guangzhou Zhongda Nansha Science and Technology Innovation Industrial Park Co., Ltd.. A kind of extraction method of saikosaponin. China Patent No. CN201610570811 2016.
[30]
Heilongjiang University Of Chinese Medicine. Method for extracting saikosaponin D from Bupleurum. China Patent No. CN201510030616 2016.
[31]
Daxinganling Lingerbei Organic Food Co., Ltd.. A kind of method for preparing saikosaponin from Bupleurum chinensis. China Patent No. CN201210595558 2013.
[32]
Qingchuan Dekangyuan Pharmaceutical Co., Ltd.. Extraction and purification method of saikosaponin A or saikosaponin D. China Patent No. CN201210143594 2014.
[33]
Song, Y.; Sun, H.; Gao, S.; Tang, K.; Zhao, Y.; Xie, G.; Gao, H. Saikosaponin a attenuates lead-induced kidney injury through activating Nrf2 signaling pathway. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2021, 242, 108945.
[http://dx.doi.org/10.1016/j.cbpc.2020.108945] [PMID: 33278595]
[34]
Chen, J.C.; Chang, N.W.; Chung, J.G.; Chen, K.C. Saikosaponin-A induces apoptotic mechanism in human breast MDA-MB-231 and MCF-7 cancer cells. Am. J. Chin. Med., 2003, 31(3), 363-377.
[http://dx.doi.org/10.1142/S0192415X03001065] [PMID: 12943168]
[35]
Wang, Q.; Zheng, X.L.; Yang, L.; Shi, F.; Gao, L.B.; Zhong, Y.J.; Sun, H.; He, F.; Lin, Y.; Wang, X. Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells. J. Exp. Clin. Cancer Res., 2010, 29(1), 159.
[http://dx.doi.org/10.1186/1756-9966-29-159] [PMID: 21143894]
[36]
Qi, X.; Liu, J.; Li, X.; Fan, M.; Huang, N.; Sun, R. Saikosaponin a contributed to CCIN treatment by promoting neutrophil bactericidal activity via activation CBL-dependent ERK pathway. Phytomedicine, 2021, 82, 153444.
[http://dx.doi.org/10.1016/j.phymed.2020.153444] [PMID: 33421903]
[37]
Wang, N.; Che, D.; Zhang, T.; Liu, R.; Cao, J.; Wang, J.; Zhao, T.; Ma, P.; Dong, X.; He, L. Saikosaponin A inhibits compound 48/80-induced pseudo-allergy via the Mrgprx2 pathway in vitro and in vivo. Biochem. Pharmacol., 2018, 148, 147-154.
[http://dx.doi.org/10.1016/j.bcp.2017.12.017] [PMID: 29274317]
[38]
Zong, Z.; Fujikawa-Yamamoto, K.; Tanino, M.; Teraoka, K.; Yamagishi, H.; Odashima, S. Saikosaponin b2-induced apoptosis of cultured B16 melanoma cell line through down-regulation of PKC activity. Biochem. Biophys. Res. Commun., 1996, 219(2), 480-485.
[http://dx.doi.org/10.1006/bbrc.1996.0259] [PMID: 8605013]
[39]
Zong, Z.; Fujikawa-Yamamoto, K.; Ota, T.; Guan, X.; Murakami, M.; Li, A.; Yamaguchi, N.; Tanino, M.; Odashima, S. Saikosaponin b2 induces differentiation without growth inhibition in cultured B16 melanoma cells. Cell Struct. Funct., 1998, 23(5), 265-272.
[http://dx.doi.org/10.1247/csf.23.265] [PMID: 9872567]
[40]
Zhao, Y.; Feng, L.; Liu, L.; Zhao, R. Saikosaponin B2 enhances the hepatotargeting effect of anticancer drugs through inhibition of multi-drug resistance-associated drug transporters. Life Sci., 2019, 231, 116557.
[http://dx.doi.org/10.1016/j.lfs.2019.116557] [PMID: 31194994]
[41]
Pan, Y.; Ke, Z.; Ye, H.; Sun, L.; Ding, X.; Shen, Y.; Zhang, R.; Yuan, J. Saikosaponin C exerts anti-HBV effects by attenuating HNF1α and HNF4α expression to suppress HBV pgRNA synthesis. Inflamm. Res., 2019, 68(12), 1025-1034.
[http://dx.doi.org/10.1007/s00011-019-01284-2] [PMID: 31531682]
[42]
Shyu, K.G.; Tsai, S.C.; Wang, B.W.; Liu, Y.C.; Lee, C.C. Saikosaponin C induces endothelial cells growth, migration and capillary tube formation. Life Sci., 2004, 76(7), 813-826.
[http://dx.doi.org/10.1016/j.lfs.2004.10.003] [PMID: 15581913]
[43]
Wang, B.; Min, W.; Lin, S.; Song, L.; Yang, P.; Ma, Q.; Guo, J. Saikosaponin-d increases radiation-induced apoptosis of hepatoma cells by promoting autophagy via inhibiting mTOR phosphorylation. Int. J. Med. Sci., 2021, 18(6), 1465-1473.
[http://dx.doi.org/10.7150/ijms.53024] [PMID: 33628104]
[44]
Ye, R.P.; Chen, Z.D. Saikosaponin A, an active glycoside from Radix bupleuri, reverses P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cells and HepG2/ADM cells. Xenobiotica, 2017, 47(2), 176-184.
[http://dx.doi.org/10.3109/00498254.2016.1171932] [PMID: 27123551]
[45]
Fu, R.; Zhang, L.; Li, Y.; Li, B.; Ming, Y.; Li, Z.; Xing, H.; Chen, J. Saikosaponin D inhibits autophagosome-lysosome fusion and induces autophagy-independent apoptosis in MDA-MB-231 breast cancer cells. Mol. Med. Rep., 2020, 22(2), 1026-1034.
[http://dx.doi.org/10.3892/mmr.2020.11155] [PMID: 32468000]
[46]
Ren, M.; McGowan, E.; Li, Y.; Zhu, X.; Lu, X.; Zhu, Z.; Lin, Y.; He, S. Saikosaponin-d suppresses COX2 through p-STAT3/C/EBPβ signaling pathway in liver cancer: A novel mechanism of action. Front. Pharmacol., 2019, 10, 623.
[http://dx.doi.org/10.3389/fphar.2019.00623] [PMID: 31191326]
[47]
Lv, Y.; Hou, X.; Zhang, Q.; Li, R.; Xu, L.; Chen, Y.; Tian, Y.; Sun, R.; Zhang, Z.; Xu, F. Untargeted metabolomics study of the in vitro anti-hepatoma effect of Saikosaponin D in combination with NRP-1 knockdown. Molecules, 2019, 24(7), E1423.
[http://dx.doi.org/10.3390/molecules24071423] [PMID: 30978940]
[48]
Yang, Y.Y.; Tang, Y.Z.; Fan, C.L.; Luo, H.T.; Guo, P.R.; Chen, J.X. Identification and determination of the saikosaponins in Radix bupleuri by accelerated solvent extraction combined with rapid-resolution LC-MS. J. Sep. Sci., 2010, 33(13), 1933-1945.
[http://dx.doi.org/10.1002/jssc.201000100] [PMID: 20512808]
[49]
Lin, T.Y.; Chiou, C.Y.; Chiou, S.J. Putative genes involved in saikosaponin biosynthesis in Bupleurum species. Int. J. Mol. Sci., 2013, 14(6), 12806-12826.
[http://dx.doi.org/10.3390/ijms140612806] [PMID: 23783277]
[50]
Wang, Y.; Zhao, L.; Han, X.; Wang, Y.; Mi, J.; Wang, C.; Sun, D.; Fu, Y.; Zhao, X.; Guo, H.; Wang, Q.; Saikosaponin, A. Saikosaponin A inhibits triple-negative breast cancer growth and metastasis through downregulation of CXCR4. Front. Oncol., 2020, 9, 1487.
[http://dx.doi.org/10.3389/fonc.2019.01487] [PMID: 32047724]
[51]
Zhang, P.; Lai, X.; Zhu, M.H.; Long, M.; Liu, X.L.; Wang, Z.X.; Zhang, Y.; Guo, R.J.; Dong, J.; Lu, Q.; Sun, P.; Fang, C.; Zhao, M. Saikosaponin A, a triterpene saponin, suppresses angiogenesis and tumor growth by blocking VEGFR2-mediated signaling pathway. Front. Pharmacol., 2021, 12, 713200.
[http://dx.doi.org/10.3389/fphar.2021.713200] [PMID: 34776948]
[52]
Li, D.Q.; Wu, J.; Liu, L.Y.; Wu, Y.Y.; Li, L.Z.; Huang, X.X.; Liu, Q.B.; Yang, J.Y.; Song, S.J.; Wu, C.F. Cytotoxic triterpenoid glycosides (saikosaponins) from the roots of Bupleurum chinense. Bioorg. Med. Chem. Lett., 2015, 25(18), 3887-3892.
[http://dx.doi.org/10.1016/j.bmcl.2015.07.053] [PMID: 26259802]
[53]
Shanghai University of Traditional Chinese Medicine. New uses of saikosaponin A. China Patent No. CN201910338996 2019.
[54]
Grivennikov, S.I.; Greten, F.R.; Karin, M. Immunity, inflammation, and cancer. Cell, 2010, 140(6), 883-899.
[http://dx.doi.org/10.1016/j.cell.2010.01.025] [PMID: 20303878]
[55]
Ma, Q.; Gao, F.F.; He, X.; Li, K.; Gao, Y.; Xu, X.L.; Jiang, N.H.; Ding, L.; Song, W.J.; He, Y.Q.; Pan, W.T.; Wei, L.; Zhang, J.W. Antitumor effects of saikosaponin b2 on breast cancer cell proliferation and migration. Mol. Med. Rep., 2019, 20(2), 1943-1951.
[http://dx.doi.org/10.3892/mmr.2019.10385] [PMID: 31257464]
[56]
Li, X.; Ke, Z.; Lian, D.; Yuan, J.; Pan, Y. Combination of saikosaponin c and telbivudine synergistically enhances the anti-HBV activity. Inflamm. Res., 2020, 69(6), 545-547.
[http://dx.doi.org/10.1007/s00011-020-01336-y] [PMID: 32313973]
[57]
Gao, T.; Zhao, P.; Yu, X.; Cao, S.; Zhang, B.; Dai, M. Use of Saikosaponin D and JNK inhibitor SP600125, alone or in combination, inhibits malignant properties of human osteosarcoma U2 cells. Am. J. Transl. Res., 2019, 11(4), 2070-2080.
[PMID: 31105818]
[58]
Wang, J.; Qi, H.; Zhang, X.; Si, W.; Xu, F.; Hou, T.; Zhou, H.; Wang, A.; Li, G.; Liu, Y.; Fang, Y.; Piao, H.L.; Liang, X. Saikosaponin D from Radix Bupleuri suppresses triple-negative breast cancer cell growth by targeting β-catenin signaling. Biomed. Pharmacother., 2018, 108, 724-733.
[http://dx.doi.org/10.1016/j.biopha.2018.09.038] [PMID: 30248540]
[59]
Chen, X.; Liu, C.; Zhao, R.; Zhao, P.; Wu, J.; Zhou, N.; Ying, M. Synergetic and antagonistic molecular effects mediated by the feedback loop of p53 and JNK between Saikosaponin D and SP600125 on lung cancer A549 cells. Mol. Pharm., 2018, 15(11), 4974-4984.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00595] [PMID: 30207732]
[60]
Li, C.; Guan, X.; Xue, H.; Wang, P.; Wang, M.; Gai, X. Reversal of P-glycoprotein-mediated multidrug resistance is induced by saikosaponin D in breast cancer MCF-7/adriamycin cells. Pathol. Res. Pract., 2017, 213(7), 848-853.
[http://dx.doi.org/10.1016/j.prp.2017.01.022] [PMID: 28554760]
[61]
Zhang, F.; Chen, L.; Jin, H.; Shao, J.; Wu, L.; Lu, Y.; Zheng, S. Activation of Fas death receptor pathway and Bid in hepatocytes is involved in saikosaponin D induction of hepatotoxicity. Environ. Toxicol. Pharmacol., 2016, 41, 8-13.
[http://dx.doi.org/10.1016/j.etap.2015.11.005] [PMID: 26645133]
[62]
Hu, S.C.; Lee, I.T.; Yen, M.H.; Lin, C.C.; Lee, C.W.; Yen, F.L. Anti-melanoma activity of Bupleurum Chinense, Bupleurum kaoi and nanoparticle formulation of their major bioactive compound saikosaponin-d. J. Ethnopharmacol., 2016, 179, 432-442.
[http://dx.doi.org/10.1016/j.jep.2015.12.058] [PMID: 26748071]
[63]
Yao, M.; Yang, J.; Cao, L.; Zhang, L.; Qu, S.; Gao, H. Saikosaponin d inhibits proliferation of DU145 human prostate cancer cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase. Mol. Med. Rep., 2014, 10(1), 365-372.
[http://dx.doi.org/10.3892/mmr.2014.2153] [PMID: 24736800]
[64]
He, S.; Lu, G.; Hou, H.; Zhao, Z.; Zhu, Z.; Lu, X.; Chen, J.; Wang, Z. Saikosaponin-d suppresses the expression of cyclooxygenase-2 through the phospho-signal transducer and activator of transcription 3/hypoxia-inducible factor-1α pathway in hepatocellular carcinoma cells. Mol. Med. Rep., 2014, 10(5), 2556-2562.
[http://dx.doi.org/10.3892/mmr.2014.2574] [PMID: 25231214]
[65]
Wang, B.F.; Wang, X.J.; Kang, H.F.; Bai, M.H.; Guan, H.T.; Wang, Z.W.; Zan, Y.; Song, L.Q.; Min, W.L.; Lin, S.; Cheng, Y.A. Saikosaponin-D enhances radiosensitivity of hepatoma cells under hypoxic conditions by inhibiting hypoxia-inducible factor-1α. Cell. Physiol. Biochem., 2014, 33(1), 37-51.
[http://dx.doi.org/10.1159/000356648] [PMID: 24401554]
[66]
Wang, B.F.; Dai, Z.J.; Wang, X.J.; Bai, M.H.; Lin, S.; Ma, H.B.; Wang, Y.L.; Song, L.Q.; Ma, X.L.; Zan, Y.; Min, W.L.; Cheng, Y.A. Saikosaponin-d increases the radiosensitivity of smmc-7721 hepatocellular carcinoma cells by adjusting the g0/g1 and g2/m checkpoints of the cell cycle. BMC Complement. Altern. Med., 2013, 13(1), 263.
[http://dx.doi.org/10.1186/1472-6882-13-263] [PMID: 24119370]
[67]
Wong, V.K.; Zhang, M.M.; Zhou, H.; Lam, K.Y.; Chan, P.L.; Law, C.K.; Yue, P.Y.; Liu, L. Saikosaponin-d enhances the anticancer potency of TNF-α via Overcoming Its Undesirable Response of Activating NF-Kappa B signalling in cancer cells. Evid. Based Complement. Alternat. Med., 2013, 2013, 745295.
[http://dx.doi.org/10.1155/2013/745295] [PMID: 23573150]
[68]
Jia, X.; Dang, S.; Cheng, Y.; Zhang, X.; Li, M.; Li, Y.; Li, S. Effects of saikosaponin-d on syndecan-2, matrix metalloproteinases and tissue inhibitor of metalloproteinases-2 in rats with hepatocellular carcinoma. J. Tradit. Chin. Med., 2012, 32(3), 415-422.
[http://dx.doi.org/10.1016/S0254-6272(13)60048-5] [PMID: 23297566]
[69]
Lu, X.L.; He, S.X.; Ren, M.D.; Wang, Y.L.; Zhang, Y.X.; Liu, E.Q. Chemopreventive effect of saikosaponin-d on diethylinitrosamine-induced hepatocarcinogenesis: Involvement of CCAAT/enhancer binding protein β and cyclooxygenase-2. Mol. Med. Rep., 2012, 5(3), 637-644.
[http://dx.doi.org/10.3892/mmr.2011.702] [PMID: 22159471]
[70]
Chen, D.S.; Mellman, I. Elements of cancer immunity and the cancer-immune set point. Nature, 2017, 541(7637), 321-330.
[http://dx.doi.org/10.1038/nature21349] [PMID: 28102259]
[71]
Demaria, O.; Cornen, S.; Daëron, M.; Morel, Y.; Medzhitov, R.; Vivier, E. Harnessing innate immunity in cancer therapy. Nature, 2019, 574(7776), 45-56.
[http://dx.doi.org/10.1038/s41586-019-1593-5] [PMID: 31578484]
[72]
Demaria, O.; Cornen, S.; Daëron, M.; Morel, Y.; Medzhitov, R.; Vivier, E. Publisher correction: Harnessing innate immunity in cancer therapy. Nature, 2019, 576(7785), E3.
[http://dx.doi.org/10.1038/s41586-019-1758-2] [PMID: 31745371]
[73]
Yang, W.; Han, W.; Qin, A.; Wang, Z.; Xu, J.; Qian, Y. The emerging role of Hippo signaling pathway in regulating osteoclast formation. J. Cell. Physiol., 2018, 233(6), 4606-4617.
[http://dx.doi.org/10.1002/jcp.26372] [PMID: 29219182]
[74]
Wang, X.; Sun, D.; Tai, J.; Chen, S.; Yu, M.; Ren, D.; Wang, L. TFAP2C promotes stemness and chemotherapeutic resistance in colorectal cancer via inactivating hippo signaling pathway. J. Exp. Clin. Cancer Res., 2018, 37(1), 27.
[http://dx.doi.org/10.1186/s13046-018-0683-9] [PMID: 29439714]
[75]
Taha, Z.; Janse van Rensburg, H.J.; Yang, X. The hippo pathway: Immunity and cancer. Cancers (Basel), 2018, 10(4), E94.
[http://dx.doi.org/10.3390/cancers10040094] [PMID: 29597279]
[76]
Moroishi, T.; Hayashi, T.; Pan, W.W.; Fujita, Y.; Holt, M.V.; Qin, J.; Carson, D.A.; Guan, K.L. The hippo pathway kinases LATS1/2 suppress cancer immunity. Cell, 2016, 167(6), 1525-1539.
[http://dx.doi.org/10.1016/j.cell.2016.11.005]
[77]
Janse van Rensburg, H.J.; Yang, X. The Hippo pathway and cancer immunity: Friend or foe? Oncoscience, 2018, 5(3-4), 49-50.
[http://dx.doi.org/10.18632/oncoscience.398] [PMID: 29854865]

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