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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

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Research Article

The In Vitro Anti-Cancer Activities of 17βH-Neriifolin Isolated from Cerbera odollam and its Binding Activity on Na+, K+-ATPase

Author(s): Nurhanan M. Yunos*, Asiah Osman, Muhammad H. Jauri, Nor J. Sallehudin and Siti Syarifah Mohd Mutalip

Volume 21, Issue 1, 2020

Page: [37 - 44] Pages: 8

DOI: 10.2174/1389201020666190917154850

Price: $65

Abstract

Background: 17βH-neriifolin, a cardiac glycoside compound had been successfully isolated from Cerbera odollam leaves based on the bioassay guided-isolation procedure. The aim of these studies were to determine the in vitro anti-cancer and binding effects of 17βH-neriifolin on Na+, K+-ATPase.

Methods: The in vitro anti-cancer effects were evaluated using Sulphorhodamine B and Hoescht 33342 assays. The Na+, K+-ATPase assay was carried out using Malachite Green assay. In silico molecular docking studies and in vitro malachite green assay were used to predict the binding activities of 17βH-neriifolin on Na+, K+-ATPase and ouabain was also included as for comparison studies.

Results: The compound was tested against breast (MCF-7, T47D), colorectal (HT-29), ovarian (A2780, SKOV-3) and skin (A375) cancer cell lines that gave IC50 values ranged from 0.022 ± 0.0015 to 0.030 ± 0.0018 μM. The mechanism of cell death of 17βH-neriifolin was further evaluated using Hoescht 33342 assay and it was found that the compound killed the cancer cells via apoptosis. 17βHneriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were - 8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively.

Conclusion: The results had confirmed the anti-proliferative effects exerted by 17βH-neriifolin in the breast, colorectal, ovarian and skin cancer cell lines. 17βH-neriifolin had shown to cause apoptotic cell death in the respective cancer cell lines.17βH-neriifolin and ouabain both bound at α-subunit in Na+, K+-ATPase and their binding energy were -8.16 ± 0.74 kcal/mol and -8.18 ± 0.48 kcal/mol respectively. This is the first report to reveal that 17βH-neriifolin managed to bind to the pocket of α-subunit of Na+.K+-ATPase.

Keywords: 17βH-neriifolin, cardiac glycoside, anti-cancer, apoptosis, Na+, K+-ATPase, ouabain.

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[1]
Wen, S.; Chen, Y.; Lu, Y.; Wang, Y.; Ding, L.; Jiang, M. Cardenolides from the Apocynaceae family and their anticancer activity. Fitoterapia, 2016, 112, 74-84.
[http://dx.doi.org/10.1016/j.fitote.2016.04.023] [PMID: 27167183]
[2]
Burkill, I.H. A dictionary of the economic products of the Malay Peninsula; , 1966. Vol. 1((A-H))
[http://dx.doi.org/http://melayu.library.uitm.edu.my/503/]
[3]
Chopra, R.N.; Nayar, S.L.; Chopra, I.C. Glossary of Indian medicinal plants; National Institute of Science Communication: New Delhi, 1956.
[4]
Chopra, R.N.; Nayar, S.L.; Handa, R.L.; Kapur, D.L. Indigenous Drugs of India; Dhur and Sons Private Ltd.: Calcutta, 1958.
[5]
Prasanth, S.S.; Rajasekaran, A. Visible spectro-photometric determination of cerberin in rat plasma. J. Appl. Pharm. Sci., 2015, 5(3), 109-112.
[http://dx.doi.org/10.7324/JAPS.2015.50319]
[6]
Laphookhieo, S.; Cheenpracha, S.; Karalai, C.; Chantrapromma, S.; Rat-a-Pa, Y.; Ponglimanont, C.; Chantrapromma, K. Cytotoxic cardenolide glycoside from the seeds of Cerbera odollam. Phytochemistry, 2004, 65(4), 507-510.
[http://dx.doi.org/10.1016/j.phytochem.2003.10.019] [PMID: 14759549]
[7]
Yamauchi, T.; Abe, F.; Wan, A.S.C. Cardenolide monoglycosides from the leaves of Cerbera odollam and Cerbera manghas (Cerbera. III). Chem. Pharm. Bull. (Tokyo), 1987, 35, 2744-2749.
[http://dx.doi.org/10.1248/cpb.35.2744]
[8]
Yamauchi, T.; Abe, F.; Wan, A.S.C. Studies on Cerbera. IV. Polar cardenolide glycosides from the leaves of Cerbera odollam and Cerbera manghas. Chem. Pharm. Bull. (Tokyo), 1987, 35, 4813-4818. b
[http://dx.doi.org/http://10.1248/cpb.35.4813]
[9]
Abe, F.; Yamauchi, T.; Wan, A.S.C. Sesqui-, sester- and trilignans from stems of Cerbera manghas and C. odollam. Phytochemistry, 1988, 27(11), 3627-3631. a
[http://dx.doi.org/10.1016/0031-9422(88)80780-5]
[10]
Abe, F.; Yamauchi, T.; Wan, A.S.C. Lignans related to olivil from genus Cerbera: Cerbera. VI. Chem. Pharm. Bull. (Tokyo), 1988, 36(2), 795-799.
[http://dx.doi.org/10.1248/cpb.36.795]
[11]
Abe, F.; Yamauchi, T.; Wan, A.S.C. Normonoterpenoids and their allopyranosides from the leaves of Cerbera species (studies on Cerbera. VIII). Chem. Pharm. Bull. (Tokyo), 1989, 37(10), 2639-2642.
[http://dx.doi.org/10.1248/cpb.37.2639]
[12]
Withering, W. An Account of the Foxglove and Some of its Medicinal Uses: With Practical Remarks on Dropsy and other Diseases; Cambridge University Press: Cambridge, 1785.
[13]
Kanji, S.; MacLean, R.D. Cardiac glycoside toxicity: More than 200 years and counting. Crit. Care Clin., 2012, 28(4), 527-535.
[http://dx.doi.org/10.1016/j.ccc.2012.07.005] [PMID: 22998989]
[14]
Newman, R.A.; Yang, P.; Pawlus, A.D.; Block, K.I. Cardiac glycosides as novel cancer therapeutic agents. Mol. Interv., 2008, 8(1), 36-49.
[http://dx.doi.org/10.1124/mi.8.1.8] [PMID: 18332483]
[15]
Elbaz, H.A.; Stueckle, T.A.; Tse, W.; Rojanasakul, Y.; Dinu, C.Z. Digitoxin and its analogs as novel cancer therapeutics. Exp. Hematol. Oncol., 2012, 1(1), 4.
[http://dx.doi.org/10.1186/2162-3619-1-4] [PMID: 23210930]
[16]
Skou, J.C. The influence of some cations on an adenosine triphosphatase from peripheral nerves. Biochim. Biophys. Acta, 1957, 23(2), 394-401.
[http://dx.doi.org/10.1016/0006-3002(57)90343-8] [PMID: 13412736]
[17]
Lingrel, J.B.; Kuntzweiler, T. Na+,K(+)-ATPase. J. Biol. Chem., 1994, 269(31), 19659-19662.
[PMID: 8051040]
[18]
Siti Syarifah, M.M.; Nurhanan, M.Y.; Muhd Haffiz, J.; Mohd Ilham, A.; Getha, K.; Asiah, O.; Norhayati, I.; Lili Sahira, H.; Anee Suryani, S. Potential anticancer compound from Cerbera odollam. J. Trop. For. Sci., 2011, 23, 89-96.
[19]
Skehan, P.; Storeng, R.; Scudiero, D.; Monks, A.; McMahon, J.; Vistica, D.; Warren, J.T.; Bokesch, H.; Kenney, S.; Boyd, M.R. New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst., 1990, 82(13), 1107-1112.
[http://dx.doi.org/10.1093/jnci/82.13.1107] [PMID: 2359136]
[20]
Nurhanan, M.Y.; Nor Azah, M.A.; Zunoliza, A.; Siti Humeriah, A.G.; Siti Syarifah, M.M.; Nor Hayati, A. In vitro anticancer activity and high-performance liquid chromatography profiles of Aquilaria subintegra fruit and seed extracts. J. Trop. For. Sci., 2017, 29(2), 37-43.
[21]
Mahbub, A.A.; Le Maitre, C.L.; Haywood-Small, S.L.; McDougall, G.J.; Cross, N.A.; Jordan-Mahy, N. Differential effects of polyphenols on proliferation and apoptosis in human myeloid and lymphoid leukemia cell lines. Anticancer. Agents Med. Chem., 2013, 13(10), 1601-1613.
[http://dx.doi.org/10.2174/18715206113139990303] [PMID: 23796248]
[22]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and autodocktools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[23]
Thomsen, R.; Christensen, M.H. MolDock: A new technique for high-accuracy molecular docking. J. Med. Chem., 2006, 49(11), 3315-3321.
[http://dx.doi.org/10.1021/jm051197e] [PMID: 16722650]
[24]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[25]
Medzihradsky, F.; Nandhasri, P.S.; Khanna, U. Enzymatic determination of cardiac glycosides. Biochem. Med., 1971, 5, 285-296.
[http://dx.doi.org/10.1016/0006-2944(71)90031-7]
[26]
Mutalip, S.S.; Yunos, N.M.; Abdul-Rahman, P.S.; Jauri, M.H.; Osman, A.; Adenan, M.I. Mechanisms of action of 17βH-neriifolin on its anticancer effect in SKOV-3 ovarian cancer cell line. Anticancer Res., 2014, 34(8), 4141-4151.
[PMID: 25075041]
[27]
Slingerland, M.; Cerella, C.; Guchelaar, H.J.; Diederich, M.; Gelderblom, H. Cardiac glycosides in cancer therapy: From preclinical investigations towards clinical trials. Invest. New Drugs, 2013, 31(4), 1087-1094.
[http://dx.doi.org/10.1007/s10637-013-9984-1] [PMID: 23748872]
[28]
Yang, P.; Menter, D.G.; Cartwright, C.; Chan, D.; Dixon, S.; Suraokar, M.; Mendoza, G.; Llansa, N.; Newman, R.A. Oleandrin-mediated inhibition of human tumor cell proliferation: Importance of Na,K-ATPase α subunits as drug targets. Mol. Cancer Ther., 2009, 8(8), 2319-2328.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-1085] [PMID: 19671733]
[29]
Ogawa, H.; Shinoda, T.; Cornelius, F.; Toyoshima, C. Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain. Proc. Natl. Acad. Sci. USA, 2009, 106(33), 13742-13747.
[http://dx.doi.org/10.1073/pnas.0907054106] [PMID: 19666591]
[30]
Morris, J.F.; Ismail-Beigi, F.; Butler, V.P.; Gati, I.; Lichtstein, D. Ouabain-sensitive Na+,K+-ATPase activity in toad brain. Comp. Biochem. Physiol. A Physiol., 1997, 118, 599-606.
[31]
Krstić, D.; Krinulović, K.; Spasojević-Tisma, V.; Joksić, G.; Momić, T.; Vasić, V. Effects of digoxin and gitoxin on the enzymatic activity and kinetic parameters of Na+/K+-ATPase. J. Enzyme Inhib. Med. Chem., 2004, 19(5), 409-415.
[http://dx.doi.org/10.1080/14756360410001722065] [PMID: 15648655]
[32]
Erdmann, E.; Hasse, W. Quantitative aspects of ouabain binding to human erythrocyte and cardiac membranes. J. Physiol., 1975, 251(3), 671-682.
[http://dx.doi.org/10.1113/jphysiol.1975.sp011115] [PMID: 127037]
[33]
Laursen, M.; Gregersen, J.L.; Yatime, L.; Nissen, P.; Fedosova, N.U. Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex. Proc. Natl. Acad. Sci. USA, 2015, 112(6), 1755-1760.
[http://dx.doi.org/10.1073/pnas.1422997112] [PMID: 25624492]

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