LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells

Niu,Qiang; Zhao,Wei; Wang,Jin; Li,Chunming; Yan,Tao; Lv,Wei; Wang,Guojing; Duan,Weihong; Zhang,Tao; Wang,Kunnan; Zhou,Dinghua

doi:10.3892/ijmm.2018.3499

LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells

Authors:
- Qiang Niu
- Wei Zhao
- Jin Wang
- Chunming Li
- Tao Yan
- Wei Lv
- Guojing Wang
- Weihong Duan
- Tao Zhang
- Kunnan Wang
- Dinghua Zhou
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Affiliations: Department of Hepatobiliary Surgery, Rocket Army General Hospital, Beijing 100088, P.R. China
Published online on: February 16, 2018 https://doi.org/10.3892/ijmm.2018.3499
Pages: 2601-2608
Copyright: © Niu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemotherapy is the best choice for the vast majority of hepatocellular carcinoma patients at late stage, but few effective chemotherapy drugs are available in clinic. Licochalcone A (LicA) is a new chemotherapy drug inducing apoptosis as Bcl-2 inhibitor, but few studies report on LicA‑induced autophagy. This study investigated the phenomenon and mechanisms of LicA-induced autophagy looking for a targeted combination drug. Human hepatocellular carcinoma cells (HCCs) were treated with LicA, to detect markers of autophagy and to investigate the mechanisms. In order to investigate the role of reactive oxygen species (ROS) in LicA‑induced autophagy, ROS, glutathione (GSH) and O2- were measured in LicA treated HCCs, and antioxidant N-Acetyl-L-cysteine (NAC) was cotreated with LicA in HCCs, then mechanisms of ROS-induced autophagy was investigated in LicA or LicA combined with NAC treated HCCs. Finally, the LicA-induced apoptosis was detected in LicA combined with NAC treated HCCs. We first report that LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, suppression of LicA-induced ROS through antioxidant NAC can enhance LicA-induced apoptosis, promoting the function of LicA killing HCCs. LicA can activate the ULK1/Atg13 complex which is upstream of autophagy, additionally, LicA also can promote ROS generation, ROS trigger the expression level of TSC1/2 complex, PRAS40, CTMP, PP2A, PDK1 and Rubicon change, these molecules are upstream of autophagy. In conclusion, LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, LicA combined with NAC can enhance LicA-induced apoptosis. Our results may provide a novel design for clinical hepatocellular carcinoma therapy trials.

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