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.