1 research outputs found
(+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks
(+)-Strebloside, a cardiac glycoside
isolated from the stem bark
of <i>Streblus asper</i> 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<sup>+</sup>/K<sup>+</sup>-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