Hsu Ren-Jun, Peng Kui-Yuan, Hsu Wen-Lin, Chen Yu-Tang, Liu Dai-Wei
Cancer Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
School of Medicine, Tzu Chi University, Hualien, Taiwan.
Front Oncol. 2022 Apr 13;12:824043. doi: 10.3389/fonc.2022.824043. eCollection 2022.
Z-ligustilide (or ligustilide) is found in () and may exert potential benefits in cancer treatment. Previous research has reported that ligustilide has anti-cancer effects on several types of cancer cells. However, studies of ligustilide on oral cancer cells have not been reported, especially under hypoxic conditions. This study focuses on the molecular mechanism of ligustilide-induced apoptosis in hypoxic oral cancer cells. We found that in hypoxic TW2.6 cells, ligustilide inhibited cell migration and induced caspase-dependent apoptosis. Accumulation of c-Myc accompanied by BH3-only members suggests that ligustilide may induce c-Myc-dependent apoptosis. In addition, we reported that ligustilide has an effect on ER-stress signaling. By using inhibitors of c-Myc, IRE1α, and ER-stress inhibitors, we found that cell morphologies or cell viability were rescued to some degree. Moreover, ligustilide is able to increase the expression of γ-H2AX and enhance the occurrence of DNA damage in oral cancer cells after radiation treatment. This result suggests that ligustilide has potential as a radiation sensitizer. Altogether, we propose that ligustilide may induce c-Myc-dependent apoptosis ER-stress signaling in hypoxic oral cancer cells.
Z-藁本内酯（或藁本内酯）存在于（）中，在癌症治疗中可能具有潜在益处。先前的研究报道藁本内酯对多种癌细胞具有抗癌作用。然而，关于藁本内酯对口腔癌细胞的研究尚未见报道，尤其是在缺氧条件下。本研究聚焦于藁本内酯诱导缺氧口腔癌细胞凋亡的分子机制。我们发现，在缺氧的TW2.6细胞中，藁本内酯抑制细胞迁移并诱导半胱天冬酶依赖性凋亡。c-Myc与仅含BH3结构域的蛋白成员的积累表明藁本内酯可能诱导c-Myc依赖性凋亡。此外，我们报道藁本内酯对内质网应激信号有影响。通过使用c-Myc抑制剂、肌醇需求酶1α（IRE1α）抑制剂和内质网应激抑制剂，我们发现细胞形态或细胞活力在一定程度上得到了挽救。此外，藁本内酯能够增加γ-H2AX的表达，并增强放疗后口腔癌细胞中DNA损伤的发生。这一结果表明藁本内酯具有作为放疗增敏剂的潜力。总之，我们提出藁本内酯可能在缺氧口腔癌细胞中诱导c-Myc依赖性凋亡和内质网应激信号。
