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

Wei Lun Chen, Yulin Ren, Jinhong Ren, Christian Erxleben, Michael E. Johnson, Saverio Gentile, A. Douglas Kinghorn, Steven M. Swanson, Joanna E. Burdette

Research output: Contribution to journalReview article

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-κB 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.

Original languageEnglish (US)
Pages (from-to)659-669
Number of pages11
JournalJournal of Natural Products
Volume80
Issue number3
DOIs
StatePublished - Mar 24 2017

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Cardiac Glycosides
Ovarian Neoplasms
Castration
Ethical Review
Molecular Docking Simulation
Moraceae
Digitoxin
MAP Kinase Signaling System
Vietnam
G2 Phase
Digoxin
Ouabain
Antineoplastic Agents
Adenosine Triphosphatases
Cell Cycle
Apoptosis
Neoplasms
In Vitro Techniques
Erythrasma
Cape Verde

ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

(+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks. / Chen, Wei Lun; Ren, Yulin; Ren, Jinhong; Erxleben, Christian; Johnson, Michael E.; Gentile, Saverio; Kinghorn, A. Douglas; Swanson, Steven M.; Burdette, Joanna E.

In: Journal of Natural Products, Vol. 80, No. 3, 24.03.2017, p. 659-669.

Research output: Contribution to journalReview article

Chen WL, Ren Y, Ren J, Erxleben C, Johnson ME, Gentile S et al. (+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks. Journal of Natural Products. 2017 Mar 24;80(3):659-669. Available from, DOI: 10.1021/acs.jnatprod.6b01150

Chen, Wei Lun; Ren, Yulin; Ren, Jinhong; Erxleben, Christian; Johnson, Michael E.; Gentile, Saverio; Kinghorn, A. Douglas; Swanson, Steven M.; Burdette, Joanna E. / (+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks.

In: Journal of Natural Products, Vol. 80, No. 3, 24.03.2017, p. 659-669.

Research output: Contribution to journalReview article

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