RRC ID 69347
Author Matsuda R, Sakagami H, Amano S, Iijima Y, Sano M, Uesawa Y, Tamura N, Oishi Y, Takeshima H.
Title Inhibition of Neurotoxicity/Anticancer Activity of Bortezomib by Caffeic Acid and Chlorogenic Acid.
Journal Anticancer Res
Abstract BACKGROUND/AIM:Bortezomib, used for the treatment of multiple myeloma, has been reported to induce potent neurotoxicity. The present study investigated whether eight popular polyphenols inhibit bortezomib-induced neurotoxicity without affecting its anticancer activity.
MATERIALS AND METHODS:Viable cell number was determined with the MTT method. Tumor-specificity was determined by the relative cytotoxicity in human oral squamous cell carcinoma vs. normal oral cells. Neurotoxicity was determined by the relative cytotoxicity in differentiated rat neuronal PC12 cells vs. normal cells. Apoptotic cells were quantified by cell cycle analysis.
RESULTS:Bortezomib induced cell shrinkage, disruption of neurites, and accumulation of PC-12 cells in subG1. Only chlorogenic acid and caffeic acid protected PC-12 cells from bortezomib-induced neurotoxicity. Ferulic acid that has one of the two hydroxyl groups replaced by a methoxy group showed a significantly reduced neuroprotective effect. Caffeic acid and the chlorogenic acid also neutralized the anticancer potential of bortezomib.
CONCLUSION:Caffeic acid and the chlorogenic acid may reduce the biological activity of bortezomib by forming a conjugate.
Volume 42(2)
Pages 781-790
Published 2022-2-1
DOI 10.21873/anticanres.15536
PII 42/2/781
PMID 35093876
MeSH Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects Bortezomib / antagonists & inhibitors Bortezomib / pharmacology* Caffeic Acids / chemistry Caffeic Acids / pharmacology* Cell Cycle / drug effects Cell Line, Tumor Cell Survival Chlorogenic Acid / chemistry Chlorogenic Acid / pharmacology* Humans Neuroprotective Agents / chemistry Neuroprotective Agents / pharmacology* PC12 Cells Polyphenols / chemistry Polyphenols / pharmacology Rats
IF 1.994
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902)