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

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 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.

Amplification of oxidative stress with lycorine and gold-based nanocomposites for synergistic cascade cancer therapy

“…TCM have been shown to possess distinct advantages over commonly used chemotherapy medicine, such as low cost, high stability and minimal side effects [ 7 , 8 ]. Lycroine (Ly), a natural active alkaloid, exhibits a wide range of pharmacological effects [ 9 – 11 ], including an excellent antitumor effect on various cancers [ 4 , 12 – 14 ]. Our previous work [ 14 ] and other two studies [ 4 , 15 ] have already confirmed that Ly possess remarkable therapeutic potential for OS.…”

“…Our previous work [ 14 ] and other two studies [ 4 , 15 ] have already confirmed that Ly possess remarkable therapeutic potential for OS. Studies suggested that antitumor effects of Ly might be associated with mitochondrial dysfunction in various types of cancer [ 12 , 15 , 16 ], including OS [ 15 ].…”

Amplification of Oxidative Stress With Lycorine and Gold-Based Nanocomposites for Synergistic Cascade Cancer Therapy

“…Our previous work [12] and other two studies [4,13] have already con rmed that Ly possess remarkable therapeutic potential for OS. Studies suggested that antitumor effects of Ly are associated with mitochondrial dysfunction in various types of cancer [10,13,14], including OS [13].…”

“…TCM have been shown to possess advantages over commonly used chemotherapy medicine, such as low cost, high stability and minimal side effects [5,6]. Lycroine (Ly), a natural active alkaloid, possesses a wide range of pharmacological effects [7][8][9], including an excellent antitumor effect on various cancers [4,[10][11][12] . Our previous work [12] and other two studies [4,13] have already con rmed that Ly possess remarkable therapeutic potential for OS.…”

“…Mitochondria, as so-called cell powerhouses, are the main intracellular sources of reactive oxygen species (ROS) [15]. Excessive ROS production, known as oxidative stress, can lead to oxidative damage and reduced mitochondrial energy production e ciency, which further increases ROS generation and causes mitochondrial damage to form a "vicious circle" [10,16,17]. However, cancer cells normally possess a powerful antioxidant system to balance the increased level of intracellular ROS [18].…”