11-epi-Sinulariolide Acetate-induced Apoptosis in Oral Cancer Cells Is Regulated by FOXO Through Inhibition of PI3K/AKT Pathway

被引:2
作者
Chang, Ting-Shou [1 ,2 ,3 ]
Lin, Jen-Jie [4 ]
Cheng, Kai-Chun [5 ,6 ,7 ]
Su, Jui-Hsin [8 ]
She, Yun-Ying [1 ]
Wu, Yu-Jen [4 ,9 ,10 ]
机构
[1] Kaohsiung Vet Gen Hosp, Dept Otolaryngol Head & Neck Surg, Kaohsiung, Taiwan
[2] Natl Def Med Ctr, Sch Med, Taipei, Taiwan
[3] Natl Cheng Kung Univ, Inst Publ Hlth, Coll Med, Tainan, Taiwan
[4] Yu Jun Biotechnol Co Ltd, Kaohsiung, Taiwan
[5] Kaohsiung Municipal Siaogang Hosp, Dept Ophthalmol, Kaohsiung, Taiwan
[6] Kaohsiung Med Univ Hosp, Dept Ophthalmol, Kaohsiung, Taiwan
[7] Kaohsiung Med Univ, Coll Med, Sch Med, Dept Ophthalmol, Kaohsiung, Taiwan
[8] Natl Museum Marine Biol & Aquarium, Pingtung, Taiwan
[9] Meiho Univ, Dept Food & Nutr, Pingtung, Taiwan
[10] Mei ho Univ, Dept Food Sci & Nutr, Pingguang Rd,23, Pingtung 91202, Taiwan
关键词
11-epi-sinulariolide acetate; oral squamous cell carcinoma; Sinularia flexibilis; PI3K; AKT; FOXO; apoptosis; CARCINOMA; TRANSCRIPTION; EPIDEMIOLOGY; PROGRESSION; EXPRESSION; RISK; AKT; NUT;
D O I
10.21873/anticanres.16429
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background/Aim: Oral cancer is a general term for carcinomas that occur around the oral tissues, and most are squamous cell carcinoma. Oral cancer is a common disease among Taiwanese males and poses a great threat to national health owing to its high mortality rate. In this study, we used the CAL-27 oral cancer cell lines as in vitro models to investigate the pathways involved in 11-epi-sinulariolide acetate (11-epi-SA)-induced apoptosis. Materials and Methods: There have been no previous studies of the anticancer activity of 11-epi-SA isolated from Sinularia flexibilis against oral cancer. We used MTT assay, cell morphologic analysis, DNA fragmentation, TUNEL/DAPI assay, and JC-1 fluorescence staining to analyze the inhibitory effect of 11-epi-SA against the CAL-27 oral cancer cell line and assessed the potential molecular mechanism of apoptosis using western blot. Results: Our results showed that 11-epi-SA inhibited CAL-27 cell proliferation, and its effect on cell growth was mediated through an apoptotic pathway mechanism. 11-epi-SA inhibited the PI3K/AKT pathway, allowing downstream FOXO to separate from 14-3-3 and return to the nucleus. We also observed that 11-epi-SA disrupted mitochondrial Bcl family protein homeostasis and activated caspase-3 and caspase-9, which led to apoptosis. Conclusion: A low concentration of 11-epi-SA can effectively induce apoptosis in oral cancer cells through the PI3K/AKT/FOXO pathway. 11-epi-SA has great potential as a new drug for the treatment of oral cancer.
引用
收藏
页码:2625 / 2634
页数:10
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