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Research ArticleExperimental Studies

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

TING-SHOU CHANG, JEN-JIE LIN, KAI-CHUN CHENG, JUI-HSIN SU, YUN-YING SHE and YU-JEN WU
Anticancer Research June 2023, 43 (6) 2625-2634; DOI: https://doi.org/10.21873/anticanres.16429
TING-SHOU CHANG
1Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.;
2School of Medicine, National Defense Medical Center, Taipei, Taiwan, R.O.C.;
3Institute of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan, R.O.C.;
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JEN-JIE LIN
4Yu Jun Biotechnology Co., Ltd., Kaohsiung, Taiwan, R.O.C.;
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KAI-CHUN CHENG
5Department of Ophthalmology, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan, R.O.C.;
6Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, R.O.C.;
7Department of Ophthalmology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, R.O.C.;
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JUI-HSIN SU
8National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, R.O.C.;
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YUN-YING SHE
1Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.;
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YU-JEN WU
4Yu Jun Biotechnology Co., Ltd., Kaohsiung, Taiwan, R.O.C.;
9Department of Food and Nutrition, Meiho University, Pingtung, Taiwan, R.O.C.
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  • For correspondence: x00002180@meiho.edu.tw
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This article has a correction. Please see:

  • Corrigendum - July 01, 2023

Abstract

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.

Key Words:
  • 11-epi-sinulariolide acetate
  • oral squamous cell carcinoma
  • Sinularia flexibilis
  • PI3K/AKT/FOXO
  • apoptosis
  • Received March 27, 2023.
  • Revision received April 8, 2023.
  • Accepted April 10, 2023.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 43 (6)
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11-epi-Sinulariolide Acetate-induced Apoptosis in Oral Cancer Cells Is Regulated by FOXO Through Inhibition of PI3K/AKT Pathway
TING-SHOU CHANG, JEN-JIE LIN, KAI-CHUN CHENG, JUI-HSIN SU, YUN-YING SHE, YU-JEN WU
Anticancer Research Jun 2023, 43 (6) 2625-2634; DOI: 10.21873/anticanres.16429

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11-epi-Sinulariolide Acetate-induced Apoptosis in Oral Cancer Cells Is Regulated by FOXO Through Inhibition of PI3K/AKT Pathway
TING-SHOU CHANG, JEN-JIE LIN, KAI-CHUN CHENG, JUI-HSIN SU, YUN-YING SHE, YU-JEN WU
Anticancer Research Jun 2023, 43 (6) 2625-2634; DOI: 10.21873/anticanres.16429
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Keywords

  • 11-epi-sinulariolide acetate
  • Oral squamous cell carcinoma
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  • apoptosis
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