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.

• Authors: Hyung-Mun Yun, Yoon-Ju Kwon, Eonmi Kim, Hea-Jong Chung, Kyung-Ran Park
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 5 (Feb 26 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 36902006 (Publication Type: Journal Article)

Chemical References

• machilin D
• Phosphatidylinositol 3-Kinases

Topics

• Humans
• Carcinoma, Squamous Cell (pathology)
• Squamous Cell Carcinoma of Head and Neck
• Phosphatidylinositol 3-Kinases
• Necroptosis
• Mouth Neoplasms (pathology)
• Apoptosis
• Autophagy (physiology)
• Head and Neck Neoplasms
• Cell Line, Tumor
• Cell Proliferation