Phthalate derivative DEHP disturbs the antiproliferative effect of camptothecin in human lung cancer cells by attenuating DNA damage and activating Akt/NF-κB signaling pathway

邻苯二甲酸酯衍生物 DEHP 通过减轻 DNA 损伤和激活 Akt/NF-κB 信号通路干扰喜树碱在人肺癌细胞中的抗增殖作用

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作者:Ritesh Urade, Chon-Kit Chou, Han-Lin Chou, Bing-Hung Chen, Tsu-Nai Wang, Eing-Mei Tsai, Chun-Tzu Hung, Shyh-Jong Wu, Chien-Chih Chiu

Abstract

Plasticizers/phthalates play a facilitating role in the development of cancer and help the tumor to grow and metastasize. Camptothecin (CPT) and its derivatives are known to have anticancer properties of inhibiting cell growth, promoting cell apoptosis, and increasing autophagy. Therefore, in this study, we investigated whether the presence of di(2-ethylhexyl) phthalate (DEHP) could hinder apoptosis and autophagy caused by CPT in non-small cell lung cancer (NSCLC) cells. We found that DEHP interferes with CPT-induced apoptosis and autophagy and increases the prosurvival pathway by reducing the DNA damage marker γ-H2AX and activating the Akt and NF-κB pathways. Furthermore, we also confirmed that combining DEHP with 3-MA has additive effects in inhibiting autophagy and apoptosis in NSCLC cells. Taken together, our findings show that DEHP could affect CPT-induced anticancer treatment and provide evidence to show that DEHP induces chemoresistance in CPT-based chemotherapy.

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