Machilin D Promotes Apoptosis and Autophagy, and Inhibits Necroptosis in Human Oral Squamous Cell Carcinoma Cells

Abstract

Oral squamous cell carcinoma (OSCC) accounts for about 90% of all head and neck cancers, the prognosis is very poor, and there are no effective targeted therapies. Herein, we isolated Machilin D (Mach), a lignin, from the roots of Saururus chinensis (S. chinensis) and assessed its inhibitory effects on OSCC. Herein, Mach had significant cytotoxicity against human OSCC cells and showed inhibitory effects against cell adhesion, migration, and invasion by inhibiting adhesion molecules, including the FAK/Src pathway. Mach suppressed the PI3K/AKT/mTOR/p70S6K pathway and MAPKs, leading to apoptotic cell death. We investigated other modes of programmed cell death in these cells and found that Mach increased LC3I/II and Beclin1 and decreased p62, leading to autophagosomes, and suppressed the necroptosis-regulatory proteins RIP1 and MLKL. Our findings provide evidence that the inhibitory effects of Mach against human YD-10B OSCC cells are related to the promotion of apoptosis and autophagy and inhibition of necroptosis and are mediated via focal adhesion molecules.

Exploring beyond Common Cell Death Pathways in Oral Cancer: A Systematic Review

“…Among the selected studies, 46 studies evaluated ferroptosis , 22 studies focused on pyroptosis [28,33,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82][83], 8 studies on necroptosis [84][85][86][87][88][89][90][91] and 5 studies on other types of cell death [92][93][94][95][96]. One study [28] explored both ferroptosis and pyroptosis, Among the selected studies, 46 studies evaluated ferroptosis , 22 studies focused on pyroptosis [28,33,[64][65][66][67][68][69][70][71][72][73]…”

Uncaria-derived alkaloids: A review on the mechanism in inducing apoptosis in oral squamous cell carcinoma

“…Meanwhile, hirsuteine has the potential to induce OSCC apoptosis by downregulating BCL-2 and upregulating CytC, BAX, APAF-1, cleavage of caspase-9 and -3 [72 -74], reducing BCL-2 expression [73], [74], and inducing cleavage of PARP [74]. Inhibition of AKT results in the activation of proapoptotic proteins, namely BAD and BAX, and subsequently triggers the activation of caspases, which are directly involved in apoptosis and forkhead box protein O1 (FOXO-1) which act as a transcription factor and regulate the proapoptotic genes expression, including BIM and Fas ligand (FasL) [79], [80]. Decreased BCL-2 expression and increased BAX expression led to a decrease in the ratio of BCL-2/BAX and increased apoptosis in OSCC [46], [81], [82].…”

Prognostic Value of Necroptosis-Related Genes Signature in Oral Squamous Cell Carcinoma

“…Oral squamous cell carcinoma (OSCC) is one of the most common head and neck malignancies with high incidence and mortality in certain parts of the world especially Asia [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Due to its potential for recurrence and metastasis, the 5-year survival rate of patients with OSCC has not been effectively improved currently [ 1 , 3 , 4 , 5 , 6 , 9 , 10 , 11 ].…”

“…Oral squamous cell carcinoma (OSCC) is one of the most common head and neck malignancies with high incidence and mortality in certain parts of the world especially Asia [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Due to its potential for recurrence and metastasis, the 5-year survival rate of patients with OSCC has not been effectively improved currently [ 1 , 3 , 4 , 5 , 6 , 9 , 10 , 11 ]. Although some progress has been made with clinical treatments such as surgery, radiotherapy, chemotherapy, and targeted therapy, the overall treatment effect of OSCC has not been significantly improved because of its particular pathogenic location, restrictions, and the highly toxic side effects of traditional therapies [ 12 , 13 ].…”

“…Xu et al suggested that knockdown of RIP1 could increase the oxaliplatin-induced apoptosis in human OSCC [ 26 ]. Yun et al proposed that the inhibitory effects of Mach against OSCC are related to the promotion of apoptosis and inhibition of necroptosis [ 9 ]. Overall, as with nonapoptotic cell death, there are still relatively few reports about necroptotic mechanisms in the treatment of OSCC [ 2 ].…”