Lycorine hydrochloride induces reactive oxygen species‑mediated apoptosis via the mitochondrial apoptotic pathway and the JNK signaling pathway in the oral squamous cell carcinoma HSC‑3 cell line

Li,Min-Hui; Liao,Xin; Li,Chen; Wang,Tian-Tian; Sun,Yi-Song; Yang,Kang; Jiang,Pei-Wen; Shi,Song-Ting; Zhang,Wen-Xin; Zhang,Kun; Li,Chao; Yang,Ping

doi:10.3892/ol.2021.12497

Lycorine hydrochloride induces reactive oxygen species‑mediated apoptosis via the mitochondrial apoptotic pathway and the JNK signaling pathway in the oral squamous cell carcinoma HSC‑3 cell line

Authors:
- Min-Hui Li
- Xin Liao
- Chen Li
- Tian-Tian Wang
- Yi-Song Sun
- Kang Yang
- Pei-Wen Jiang
- Song-Ting Shi
- Wen-Xin Zhang
- Kun Zhang
- Chao Li
- Ping Yang
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Affiliations: Center of Science and Research, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, School of Bioscience and Technology, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, School of Basic Medicine, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, School of Laboratory Medicine, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, Department of Head and Neck Surgery, Sichuan Cancer Hospital and Institute, Chengdu, Sichuan 610041, P.R. China
Published online on: January 26, 2021 https://doi.org/10.3892/ol.2021.12497
Article Number: 236
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Poor drug efficacy is a prominent cause of oral squamous cell carcinoma (OSCC) treatment failure. Although increased efforts in developing OSCC therapeutic strategies have been achieved in recent decades, the 5‑year survival rate of patients with OSCC remains poor and effective drugs to treat OSCC are lacking. The aim of the present study was to investigate the apoptotic effect caused by lycorine hydrochloride (LH) and to identify its mechanism in the OSCC HSC‑3 cell line. The findings demonstrated that LH effectively induced HSC‑3 cell apoptosis and cell cycle arrest at the G0/G1 phase, resulting in the inhibition of cell proliferation. Furthermore, it was found that LH increased reactive oxygen species (ROS) production, triggered mitochondrial membrane potential (MMP) disorder, enhanced the protein expression levels of Bax, Bim, cleaved caspase‑9, caspase‑3 and poly(ADP‑ribose) polymerase 1 and decreased Mcl‑1 expression. The protein expression levels of important members of the JNK signaling pathway, including phosphorylated (p)‑JNK, p‑mitogen‑activated protein kinase kinase 4 and p‑c‑Jun, were significantly increased in LH‑treated cells, accompanied by an increase in ROS. However, N‑acetyl cysteine (NAC), a potent antioxidant, reversed the upregulated mRNA expression of c‑Jun, as well as the enhanced ROS production, the disorder of MMP and the apoptosis of HSC‑3 cells induced by LH. These results suggested that LH may induce HSC‑3 cell apoptosis via the ROS‑mediated mitochondrial apoptotic pathway and the JNK signaling pathway, which indicated that LH may be a potential drug candidate for anti‑OSCC therapy.

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