(+)-Strebloside-Induced Cytotoxicity in Ovarian Cancer Cells Is Mediated through Cardiac Glycoside Signaling Networks
| Autor: | Christian Erxleben, Steven M. Swanson, Jinhong Ren, A. Douglas Kinghorn, Yulin Ren, Joanna E. Burdette, Saverio Gentile, Wei Lun Chen, Michael E. Johnson |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Digoxin Digitoxin Pharmaceutical Science Streblus asper Apoptosis Pharmacology Biology Carcinoma Ovarian Epithelial Article Analytical Chemistry Cardiac Glycosides 03 medical and health sciences 0302 clinical medicine Drug Discovery medicine Humans Neoplasms Glandular and Epithelial Cytotoxicity Ouabain Cardiac glycoside Uncategorized Ovarian Neoplasms Molecular Structure Organic Chemistry NF-kappa B Biological activity Stereoisomerism biology.organism_classification Molecular biology Antineoplastic Agents Phytogenic In vitro 030104 developmental biology Complementary and alternative medicine 030220 oncology & carcinogenesis Molecular Medicine Female Sodium-Potassium-Exchanging ATPase HT29 Cells medicine.drug Signal Transduction |
| DOI: | 10.25417/uic.19719808 |
| Popis: | (+)-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|