TY - JOUR
T1 - An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs
AU - Tian, Tian
AU - Inoue, Kanako
AU - Chiba, Yuta
AU - Funada, Keita
AU - Yuta, Tomomi
AU - Mizuta, Kanji
AU - Fu, Yao
AU - Kawahara, Jumpei
AU - Han, Xue
AU - Ando, Yuna
AU - Funada, Ami
AU - Yamada, Aya
AU - Iwamoto, Tsutomu
AU - Nakamura, Seiji
AU - Takahashi, Ichiro
AU - Fukumoto, Satoshi
AU - Yoshizaki, Keigo
N1 - Funding Information:
We thank DNAFORM (Yokohama, Japan) for technical assistance in performing CAGE analysis. We also appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (18H03012, 21H03150 to K.Y. and 17H01606 to S.F.). This work was supported by JST FOREST Program (JPMJFR2013 to K. Y.). K. Y. was supported by a Takeda Science Foundation. T. T. was a JSPS Research Fellow of DC2 and supported by an Otsuka-Toshimi Scholarship.
Funding Information:
We thank DNAFORM (Yokohama, Japan) for technical assistance in performing CAGE analysis. We also appreciate the technical assistance from The Research Support Center, Research Center for Human Disease Modeling, Kyushu University Graduate School of Medical Sciences. This study was supported by a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) KAKENHI (18H03012, 21H03150 to K.Y. and 17H01606 to S.F.). This work was supported by JST FOREST Program (JPMJFR2013 to K. Y.). K. Y. was supported by a Takeda Science Foundation. T. T. was a JSPS Research Fellow of DC2 and supported by an Otsuka-Toshimi Scholarship.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-022-06945-7
DO - 10.1038/s41598-022-06945-7
M3 - Article
C2 - 35197531
AN - SCOPUS:85125213079
SN - 2045-2322
VL - 12
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 3093
ER -
