Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Republic of Korea.
National Development Institute for Korean Medicine, Gyeongsan 38540, Republic of Korea.
Int J Mol Sci. 2023 Feb 26;24(5):4576. doi: 10.3390/ijms24054576.
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 () 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.
口腔鳞状细胞癌（OSCC）约占所有头颈部癌症的 90%，预后非常差，且目前尚无有效的靶向治疗方法。在此，我们从（）的根部分离出木栓醇（Mach），一种木质素，并评估了其对 OSCC 的抑制作用。木栓醇对人 OSCC 细胞具有显著的细胞毒性，并通过抑制黏附分子（包括 FAK/Src 通路）显示出对细胞黏附、迁移和侵袭的抑制作用。木栓醇抑制 PI3K/AKT/mTOR/p70S6K 通路和 MAPKs，导致细胞凋亡死亡。我们在这些细胞中研究了其他程序性细胞死亡模式，并发现木栓醇增加了 LC3I/II 和 Beclin1，同时降低了 p62，导致自噬体形成，并抑制了坏死性凋亡调节蛋白 RIP1 和 MLKL。我们的研究结果表明，木栓醇对人 YD-10B OSCC 细胞的抑制作用与促进细胞凋亡和自噬以及抑制坏死性凋亡有关，是通过黏附斑分子介导的。
