Protection of Bortezomib-induced Neurotoxicity by Antioxidants.

Abstract

BACKGROUND/AIM:

Although chemotherapy agents, such as oxaliplatin, cisplatin, paclitaxel and bortezomib frequently cause severe peripheral neuropathy, very few studies have reported the effective strategy to prevent this side effect. In this study, we first investigated whether these drugs show higher neuropathy compared to a set of 15 other anticancer drugs, and then whether antioxidants, such as sodium ascorbate, N-acetyl-L-cysteine, and vitamin B12 have any protective effect against them.

MATERIALS AND METHODS:

Rat PC12 cells were induced to differentiate into neuronal cells by repeated overlay of serum-free medium supplemented with nerve growth factor. The cytotoxic levels of anticancer drugs against four human oral squamous cell carcinoma cell lines, three normal oral cells, and undifferentiated and differentiated PC12 cells were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cells were sorted for apoptotic cells (distributed into subG1 phase) and cells at different stages of cell cycle (G1, S and G2/M).

RESULTS:

All 19 anticancer drugs showed higher cytotoxicity against PC12 compared to oral normal cells. Among them, bortezomib showed the highest cytotoxicity against both undifferentiated and differentiated PC12 cell and, committed them to undergo apoptosis. Sodium ascorbate and N-acetyl-L-cysteine, but not vitamin B12, completely reversed the cytotoxicity of bortezomib.

CONCLUSION:

Bortezomib-induced neuropathy might be ameliorated by antioxidants.

• Authors: Yosuke Iijima, Kenjiro Bandow, Shigeru Amano, Motohiko Sano, Shunsuke Hino, Takahiro Kaneko, Norio Horie, Hiroshi Sakagami
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 7 Pg. 3685-3696 (Jul 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 32620607 (Publication Type: Journal Article)
• Copyright: Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Antioxidants
• Bortezomib
• Nerve Growth Factor

Topics

• Animals
• Antineoplastic Agents (adverse effects, pharmacology)
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Bortezomib (adverse effects, pharmacology)
• Carcinoma, Squamous Cell (drug therapy, metabolism)
• Cell Cycle (drug effects)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Humans
• Mouth Neoplasms (drug therapy, metabolism)
• Nerve Growth Factor (metabolism)
• Neurons (drug effects, metabolism)
• Neurotoxicity Syndromes (drug therapy, metabolism)
• PC12 Cells
• Peripheral Nervous System Diseases (chemically induced, drug therapy, metabolism)
• Rats