An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs

Tian Tian, Kanako Miyazaki, Yuta Chiba, Keita Funada, Tomomi Yuta, Kanji Mizuta, Yao Fu, Jumpei Kawahara, Xue Han, Yuna Ando, Ami Funada, Aya Yamada, Tsutomu Iwamoto, Seiji Nakamura, Ichiro Takahashi, Satoshi Fukumoto, Keigo Yoshizaki

研究成果: Article査読

抄録

Development of chemotherapy has led to a high survival rate of cancer patients; however, the severe side effects of anticancer drugs, including organ hypoplasia, persist. To assume the side effect of anticancer drugs, we established a new ex vivo screening model and described a method for suppressing side effects. Cyclophosphamide (CPA) is a commonly used anticancer drug and causes severe side effects in developing organs with intensive proliferation, including the teeth and hair. Using the organ culture model, we found that treatment with CPA disturbed the growth of tooth germs by inducing DNA damage, apoptosis and suppressing cellular proliferation and differentiation. Furthermore, low temperature suppressed CPA-mediated inhibition of organ development. Our ex vivo and in vitro analysis revealed that low temperature impeded Rb phosphorylation and caused cell cycle arrest at the G1 phase during CPA treatment. This can prevent the CPA-mediated cell damage of DNA replication caused by the cross-linking reaction of CPA. Our findings suggest that the side effects of anticancer drugs on organ development can be avoided by maintaining the internal environment under low temperature.

本文言語English
論文番号3093
ジャーナルScientific reports
12
1
DOI
出版ステータスPublished - 2022 12月

ASJC Scopus subject areas

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