PT - JOURNAL ARTICLE AU - REONA MATSUDA AU - HIROSHI SAKAGAMI AU - SHIGERU AMANO AU - YOSUKE IIJIMA AU - MOTOHIKO SANO AU - YOSHIHIRO UESAWA AU - NOBUAKI TAMURA AU - YOHEI OISHI AU - HIROSHI TAKESHIMA TI - Inhibition of Neurotoxicity/Anticancer Activity of Bortezomib by Caffeic Acid and Chlorogenic Acid AID - 10.21873/anticanres.15536 DP - 2022 Feb 01 TA - Anticancer Research PG - 781--790 VI - 42 IP - 2 4099 - http://ar.iiarjournals.org/content/42/2/781.short 4100 - http://ar.iiarjournals.org/content/42/2/781.full SO - Anticancer Res2022 Feb 01; 42 AB - 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.