p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities

著者: Jie Li, Pingyuan Wang, Nathaniel Long, Jie Zhuang, Danielle Springer, Jizhong Zou, Yongshun Lin, Christopher K. E. Bleck, Jihoon Park, Ju‐Gyeong Kang, Paul M. Hwang - Proceedings of the National Academy of Sciences, PNAS 2019 被引用: 84

Significance Doxorubicin is a DNA-damaging agent that is highly effective against various types of cancers, but a subset of treated patients develop heart failure for unclear genetic reasons. In the current study using p53 mouse models, low-dose doxorubicin as administered in the clinics surprisingly revealed that the absence of p53 increases susceptibility to doxorubicin cardiotoxicity while a mutant of p53 that retains mitochondrial regulation is protective. Notably, promoting mitochondrial biogenesis with a simple vitamin supplement ameliorated the cardiotoxicity. Furthermore, mitochondrial blood markers observed in association with doxorubicin susceptibility could provide guidance for the safer use of this effective chemotherapy.