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

Ting-Shou Chang1,2,3, Jen-Jie Lin4, Kai-Chun Cheng5,6,7

  • 1Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, R.O.C.

Anticancer Research
|May 29, 2023
PubMed
Abstract

Insights

11-epi-sinulariolide acetate (11-epi-SA) induces apoptosis in oral cancer cells by inhibiting the PI3K/AKT/FOXO pathway. This compound shows promise as a novel therapeutic agent for oral cancer treatment.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Oncology

Background:

  • Oral cancer, primarily squamous cell carcinoma, is a significant health concern in Taiwan, particularly among males, due to its high mortality rate.
  • 11-epi-sinulariolide acetate (11-epi-SA), a compound isolated from Sinularia flexibilis, has not been previously investigated for its anticancer effects on oral cancer.

Purpose of the Study:

  • To investigate the in vitro anticancer activity of 11-epi-SA against the CAL-27 oral cancer cell line.
  • To elucidate the molecular mechanisms underlying 11-epi-SA-induced apoptosis in oral cancer cells.

Main Methods:

  • MTT assay for cell proliferation inhibition.
  • Morphological analysis, DNA fragmentation, TUNEL/DAPI, and JC-1 staining to assess apoptosis.
  • Western blot analysis to investigate key apoptotic pathway proteins.

Main Results:

  • 11-epi-SA demonstrated significant inhibition of CAL-27 oral cancer cell proliferation.
  • The compound induced apoptosis via the PI3K/AKT/FOXO signaling pathway, leading to FOXO nuclear translocation.
  • 11-epi-SA disrupted mitochondrial homeostasis and activated caspase-3 and caspase-9, key executioners of apoptosis.

Conclusions:

  • 11-epi-SA effectively induces apoptosis in oral cancer cells at low concentrations through the PI3K/AKT/FOXO pathway.
  • 11-epi-SA exhibits considerable potential as a novel therapeutic candidate for oral cancer treatment.
Keywords:
11-epi-sinulariolide acetatePI3K/AKT/FOXOSinularia flexibilisapoptosisoral squamous cell carcinoma

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