Pectolinarigenin inhibits bladder urothelial carcinoma cell proliferation by regulating DNA damage/autophagy pathways
Zhao Deng, Dexin Shen, Mengxue Yu, Fenfang Zhou, Danni Shan, Yayun Fang, Wan Jin, Kaiyu Qian, Shenjuan Li, Gang Wang, Yi Zhang, Lingao Ju, Yu Xiao, Xinghuan Wang
Abstract
Pectolinarigenin (PEC), an active compound isolated from traditional herbal medicine, has shown potential anti-tumor properties against various types of cancer cells. However, its mechanism of action in bladder cancer (BLCA), which is one of the fatal human carcinomas, remains unexplored. In this study, we first revealed that PEC, as a potential DNA topoisomerase II alpha (TOP2A) poison, can target TOP2A and cause significant DNA damage. PEC induced G2/M phase cell cycle arrest via p53 pathway. Simultaneously, PEC can perform its unique function by inhibiting the late autophagic flux. The blocking of autophagy caused proliferation inhibition of BLCA and further enhanced the DNA damage effect of PEC. In addition, we proved that PEC could intensify the cytotoxic effect of gemcitabine (GEM) on BLCA cells in vivo and in vitro. Summarily, we first systematically revealed that PEC had great potential as a novel TOP2A poison and an inhibitor of late autophagic flux in treating BLCA.