title: Establishment of a Novel In Vitro Model for Predicting Incidence and Severity of Microtubule-targeting Agent-induced Peripheral Neuropathy.
abstract: Peripheral neuropathy (PN) is a major dose-limiting side-effect of microtubule-targeting agents (MTAs), considered to be induced by inhibition of axonal microtubules. Therefore, it was thought that a useful method for predicting the frequencies of severe sensory-PN (FPN) would be to evaluate the neurite-disrupting effects of MTAs. Using neurite outgrowth from neuron-like cell lines, we comprehensively evaluated the neurite-disrupting effects of several anti-cancer drugs including MTAs, and the reversibility of the effects of MTAs. MTAs that induce PN showed neurite-disrupting effects more strongly than MTAs and anticancer drugs that do not induce PN, but the effects were not related to the FPN. On the other hand, MTAs with high FPN exhibited lower reversibility than those with low FPN. These findings suggest that neurite-disrupting effects are associated with the incidence of PN, and the reversibility of the effects is associated with FPN.
authors.affiliation: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi-shi, Tokyo, Japan yuichi-sawaguchi@yakult.co.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sawaguchi
authors.affiliation: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi-shi, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ueno
authors.affiliation: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi-shi, Tokyo, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nishiyma
authors.affiliation: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi-shi, Tokyo, Japan.
authors.forename: Ryuta
authors.initials: R
authors.lastname: Yamazaki
authors.affiliation: Yakult Central Institute for Microbiological Research, Yakult Honsha Co., Ltd., Kunitachi-shi, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsuzaki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D006801:Humans; D015994:Incidence; D008870:Microtubules / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects*; D016716:PC12 Cells; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents
keywords: PC-12 cells; Peripheral neuropathy; SH-SY5Y cells; in vitro model; microtubule-targeting agents; neurite-distupting effects