Chang Yung-Ting, Wu Chang-Yi, Tang Jen-Yang, Huang Chiung-Yao, Liaw Chih-Chuang, Wu Shih-Hsiung, Sheu Jyh-Horng, Chang Hsueh-Wei
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.
Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei, 11529, Taiwan.
Environ Toxicol. 2017 Sep;32(9):2124-2132. doi: 10.1002/tox.22425. Epub 2017 May 26.
Soft corals-derived natural product, sinularin, was antiproliferative against some cancers but its effect and detailed mechanism on oral cancer cells remain unclear. The subject of this study is to examine the antioral cancer effects and underlying detailed mechanisms in terms of cell viability, oxidative stress, cell cycle analysis, and apoptosis analyses. In MTS assay, sinularin dose-responsively decreased cell viability of three oral cancer cells (Ca9-22, HSC-3, and CAL 27) but only little damage to oral normal cells (HGF-1). This cell killing effect was rescued by the antioxidant N-acetylcysteine (NAC) pretreatment. Abnormal cell morphology and induction of reactive oxygen species (ROS) were found in sinularin-treated oral cancer Ca9-22 cells, however, NAC pretreatment also recovered these changes. Sinularin arrested the Ca9-22 cells at G2/M phase and dysregulated the G2/M regulatory proteins such as cdc2 and cyclin B1. Sinularin dose-responsively induced apoptosis on Ca9-22 cells in terms of flow cytometry (annexin V and pancaspase analyses) and western blotting (caspases 3, 8, 9) and poly (ADP-ribose) polymerase (PARP). These apoptotic changes of sinularin-treated Ca9-22 cells were rescued by NAC pretreatment. Taken together, sinularin induces oxidative stress-mediated antiproliferation, G2/M arrest, and apoptosis against oral cancer cells and may be a potential marine drug for antioral cancer therapy.
源自软珊瑚的天然产物西松烯对某些癌症具有抗增殖作用，但其对口腔癌细胞的作用及详细机制尚不清楚。本研究的主题是从细胞活力、氧化应激、细胞周期分析和凋亡分析等方面研究其抗口腔癌作用及潜在的详细机制。在MTS检测中，西松烯剂量依赖性地降低了三种口腔癌细胞（Ca9-22、HSC-3和CAL 27）的细胞活力，但对口腔正常细胞（HGF-1）的损伤很小。抗氧化剂N-乙酰半胱氨酸（NAC）预处理可挽救这种细胞杀伤作用。在经西松烯处理的口腔癌Ca9-22细胞中发现了异常的细胞形态和活性氧（ROS）的诱导，然而，NAC预处理也恢复了这些变化。西松烯使Ca9-22细胞停滞在G2/M期，并使G2/M调节蛋白如cdc2和细胞周期蛋白B1失调。从流式细胞术（膜联蛋白V和泛半胱天冬酶分析）和蛋白质印迹法（半胱天冬酶3、8、9）以及聚（ADP-核糖）聚合酶（PARP）来看，西松烯剂量依赖性地诱导Ca9-22细胞凋亡。NAC预处理可挽救经西松烯处理的Ca9-22细胞的这些凋亡变化。综上所述，西松烯可诱导氧化应激介导的抗增殖、G2/M期阻滞和对口腔癌细胞的凋亡，可能是一种潜在的抗口腔癌海洋药物。
