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Title: Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
Authors: Imai, Satoshi
Koyanagi, Madoka
Azimi, Ziauddin
Nakazato, Yui
Matsumoto, Mayuna
Ogihara, Takashi
Yonezawa, Atsushi  kyouindb  KAKEN_id  orcid (unconfirmed)
Omura, Tomohiro  kyouindb  KAKEN_id
Nakagawa, Shunsaku  kyouindb  KAKEN_id
Wakatsuki, Shuji
Araki, Toshiyuki
Kaneko, Shuji
Nakagawa, Takayuki  kyouindb  KAKEN_id
Matsubara, Kazuo
Author's alias: 今井, 哲司
米澤, 淳
金子, 周司
中川, 貴之
松原, 和夫
Keywords: Schwann cell
Somatic system
Issue Date: 20-Jul-2017
Publisher: Springer Nature
Journal title: Scientific reports
Volume: 7
Thesis number: 5947
Abstract: Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons. Similarly, these anti-cancer drugs disrupted myelin formation in Schwann cell/DRG neuron co-cultures without affecting nerve axons. Cisplatin and oxaliplatin, but not paclitaxel, caused mitochondrial dysfunction in cultured Schwann cells. By contrast, paclitaxel led to dedifferentiation of Schwann cells into an immature state, characterized by increased expression of p75 and galectin-3. Consistent with in vitro findings, repeated injection of paclitaxel increased expression of p75 and galectin-3 in Schwann cells within the mouse sciatic nerve. These results suggest that taxanes and platinum derivatives impair Schwan cells by inducing dedifferentiation and mitochondrial dysfunction, respectively, which may be important in the development of CIPN in conjunction with their direct impairment in peripheral neurons.
Rights: © The Author(s) 2017
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41598-017-05784-1
PubMed ID: 28729624
Appears in Collections:Journal Articles

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