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Delayed treatment with vitamin C and N-acetyl-L: -cysteine protects Schwann cells without compromising the anti-myeloma activity of bortezomib.
MedLine Citation:
PMID:  21526377     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Bortezomib-induced peripheral neuropathy (BIPN) emerges as a disabling adverse effect. As rat models for BIPN have demonstrated damage in nerve Schwann cells, we screened for cytoprotective agents to devise a method of rescuing Schwann cells from the cytotoxic effects of bortezomib without compromising its anti-myeloma effects. Schwann cells underwent macroautophagy along with cytoplasmic inclusion body and vacuole formation, and appeared much less susceptible to bortezomib-induced cytotoxicity than did myeloma cells. Vitamin C or N-acetyl-L: -cysteine (NAC) achieved near-complete rescue of Schwann cells treated with bortezomib at 30 nM or less, and these agents in combination are able to cooperatively inhibit the morphological changes and the cytotoxicity in Schwann cells with higher doses of bortezomib. The delayed addition of vitamin C and/or NAC after the exposure to bortezomib alleviated the cytotoxicity in Schwann cells but not myeloma cells. These results suggest that delayed treatment with these agents may be instrumental in prophylaxis of BIPN.
Authors:
Ayako Nakano; Masahiro Abe; Asuka Oda; Hiroe Amou; Masahiro Hiasa; Shingen Nakamura; Hirokazu Miki; Takeshi Harada; Shirou Fujii; Kumiko Kagawa; Kyoko Takeuchi; Takashi Watanabe; Shuji Ozaki; Toshio Matsumoto
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-28
Journal Detail:
Title:  International journal of hematology     Volume:  -     ISSN:  1865-3774     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan.
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