Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

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...

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Autores principales:	Satoshi Imai, Madoka Koyanagi, Ziauddin Azimi, Yui Nakazato, Mayuna Matsumoto, Takashi Ogihara, Atsushi Yonezawa, Tomohiro Omura, Shunsaku Nakagawa, Shuji Wakatsuki, Toshiyuki Araki, Shuji Kaneko, Takayuki Nakagawa, Kazuo Matsubara
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96a74b95e0a94d778ade5e72e0779709
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spelling	oai:doaj.org-article:96a74b95e0a94d778ade5e72e07797092021-12-02T11:40:32ZTaxanes and platinum derivatives impair Schwann cells via distinct mechanisms10.1038/s41598-017-05784-12045-2322https://doaj.org/article/96a74b95e0a94d778ade5e72e07797092017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05784-1https://doaj.org/toc/2045-2322Abstract 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.Satoshi ImaiMadoka KoyanagiZiauddin AzimiYui NakazatoMayuna MatsumotoTakashi OgiharaAtsushi YonezawaTomohiro OmuraShunsaku NakagawaShuji WakatsukiToshiyuki ArakiShuji KanekoTakayuki NakagawaKazuo MatsubaraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Satoshi Imai Madoka Koyanagi Ziauddin Azimi Yui Nakazato Mayuna Matsumoto Takashi Ogihara Atsushi Yonezawa Tomohiro Omura Shunsaku Nakagawa Shuji Wakatsuki Toshiyuki Araki Shuji Kaneko Takayuki Nakagawa Kazuo Matsubara Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
description	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.
format	article
author	Satoshi Imai Madoka Koyanagi Ziauddin Azimi Yui Nakazato Mayuna Matsumoto Takashi Ogihara Atsushi Yonezawa Tomohiro Omura Shunsaku Nakagawa Shuji Wakatsuki Toshiyuki Araki Shuji Kaneko Takayuki Nakagawa Kazuo Matsubara
author_facet	Satoshi Imai Madoka Koyanagi Ziauddin Azimi Yui Nakazato Mayuna Matsumoto Takashi Ogihara Atsushi Yonezawa Tomohiro Omura Shunsaku Nakagawa Shuji Wakatsuki Toshiyuki Araki Shuji Kaneko Takayuki Nakagawa Kazuo Matsubara
author_sort	Satoshi Imai
title	Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
title_short	Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
title_full	Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
title_fullStr	Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
title_full_unstemmed	Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms
title_sort	taxanes and platinum derivatives impair schwann cells via distinct mechanisms
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/96a74b95e0a94d778ade5e72e0779709
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Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

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