RT Journal Article
SR Electronic
T1 11-<em>epi</em>-Sinulariolide Acetate-induced Apoptosis in Oral Cancer Cells Is Regulated by FOXO Through Inhibition of PI3K/AKT Pathway
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2625
OP 2634
DO 10.21873/anticanres.16429
VO 43
IS 6
A1 CHANG, TING-SHOU
A1 LIN, JEN-JIE
A1 CHENG, KAI-CHUN
A1 SU, JUI-HSIN
A1 SHE, YUN-YING
A1 WU, YU-JEN
YR 2023
UL http://ar.iiarjournals.org/content/43/6/2625.abstract
AB 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.