Oncotarget

Research Papers:

Activation of endoplasmic reticulum stress and the extrinsic apoptotic pathway in human lung cancer cells by the new synthetic flavonoid, LZ-205

Yi Zhang, Xuefen Xu, Wei Li, Hanchi Miao, Shaoliang Huang, Yuxin Zhou, Yang Sun, Zhiyu Li, Qinglong Guo and Li Zhao _

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Oncotarget. 2016; 7:87257-87270. https://doi.org/10.18632/oncotarget.13535

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Abstract

Yi Zhang1,*, Xuefen Xu1,*, Wei Li1, Hanchi Miao1, Shaoliang Huang1, Yuxin Zhou1, Yang Sun1, Zhiyu Li2, Qinglong Guo1, Li Zhao1

1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, People’s Republic of China

2School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Qinglong Guo, email: [email protected]

Li Zhao, email: [email protected]

Keywords: LZ-205, apoptosis, ER stress, ROS, extrinsic apoptosis

Received: March 17, 2016    Accepted: November 02, 2016    Published: November 24, 2016

ABSTRACT

It has been shown that flavonoids have anti-tumor activity. In this study, LZ-205, a newly synthesized flavonoid, was found to be effective in inducing apoptosis in human lung cancer cells in vivo and in vitro. Mechanistically, LZ-205 triggers reactive oxygen species (ROS)-induced endoplasmic reticulum (ER) stress and unfolded protein response, which could be reversed by silencing CHOP, a mediator of the ER stress-associated apoptosis. In addition, LZ-205-induced apoptosis is accompanied by the activation of both the mitochondrial apoptotic and extrinsic pathways, followed by decreased mitochondrial membrane potential (ΔΨm) and the alteration of the expression of mitochondria-related pro- and anti-apoptotic proteins. LZ-205 exhibits a potential antitumor effect in BALB/c nude mice bearing H460 tumor with low systemic toxicity. In summary, both the ROS-mediated ER stress pathway and the exogenous apoptotic pathway are involved in LZ-205-induced apoptosis in vitro and in vivo. Our data show a therapeutic potential of LZ-205 for the treatment of lung cancer.


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