(+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks Journal Article

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Authors: Chen, W. L.; Ren, Y.; Ren, J.; Erxleben, C.; Johnson, M. E.; Gentile, S; Kinghorn, A. D.; Swanson, S. M.; Burdette, J. E.
Article Title: (+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks
Abstract: (+)-Strebloside, a cardiac glycoside isolated from the stem bark of Streblus asper collected in Vietnam, has shown some potential for further investigation as an antineoplastic agent. A mechanistic study using an in vitro assay and molecular docking analysis indicated that (+)-strebloside binds and inhibits Na+/K+-ATPase in a similar manner to digitoxin. Inhibition of growth of different high-grade serous ovarian cancer cells including OVCAR3, OVSAHO, Kuramochi, OVCAR4, OVCAR5, and OVCAR8 resulted from treatment with (+)-strebloside. Furthermore, this compound blocked cell cycle progression at the G2 phase and induced PARP cleavage, indicating apoptosis activation in OVCAR3 cells. (+)-Strebloside potently inhibited mutant p53 expression through the induction of ERK pathways and inhibited NF-kappaB activity in human ovarian cancer cells. However, in spite of its antitumor potential, the overall biological activity of (+)-strebloside must be regarded as being typical of better-known cardiac glycosides such as digoxin and ouabain. Further chemical alteration of cardiac glycosides might help to reduce negative side effects while increasing cancer cell cytotoxicity.
Journal Title: Journal of natural products
Volume: 80
Issue: 3
ISSN: 1520-6025; 0163-3864
Publisher: Unknown  
Journal Place: United States
Date Published: 2017
Start Page: 659
End Page: 669
Language: eng
DOI/URL:

10.1021/acs.jnatprod.6b01150
Notes: LR: 20170324; JID: 7906882; ppublish