Journal
ONCOLOGY LETTERS
Volume 21, Issue 3, Pages -Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ol.2021.12497
Keywords
lycorine hydrochloride; oral squamous cell carcinoma; apoptosis; reactive oxygen species; mitochondrial apoptotic pathway; JNK signaling pathway
Categories
Funding
- Key Research and Development Program [20ZDYFS0321]
- Applied Basic Research Program of Science and Technology Department of Sichuan Province [2017JY0173]
- Research and Innovation Fund for Postgraduates of Chengdu Medical College [YCX2020-16]
- National Undergraduates Innovating Experimentation Project of China [201713705007, 201713705009, 201813705002, 201913705003]
- National Natural Science Foundation of China [81872451]
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The poor drug efficacy is a primary cause of treatment failure in oral squamous cell carcinoma (OSCC). Despite efforts in developing therapeutic strategies for OSCC, effective drugs are still lacking and the 5-year survival rate of patients with OSCC is low. The study investigated the apoptotic effect of lycorine hydrochloride (LH) on OSCC HSC-3 cell line, demonstrating that LH induced cell apoptosis and cell cycle arrest, inhibited cell proliferation, and activated ROS-mediated mitochondrial apoptotic pathway and JNK signaling pathway in OSCC cells, suggesting LH as a potential drug candidate for anti-OSCC therapy.
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 G(0)/G(1) 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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