2. Academic Validation
  3. Cyclocommunol induces apoptosis in human oral squamous cell carcinoma partially through a Mcl-1-dependent mechanism

Cyclocommunol induces apoptosis in human oral squamous cell carcinoma partially through a Mcl-1-dependent mechanism

  • Phytomedicine. 2018 Jan 15;39:25-32. doi: 10.1016/j.phymed.2017.12.004.
Jing-Ru Weng 1,  Li-Yuan Bai 2,  Horng-Huey Ko 3,  Yi-Tung Tsai 4
Affiliations

Affiliations

  • 1 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. Electronic address: [email protected].
  • 2 College of Medicine, China Medical University, Taichung 40402, Taiwan; Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung 40447, Taiwan.
  • 3 Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80715, Taiwan.
  • 4 Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan.
PMID: 29433680 DOI: 10.1016/j.phymed.2017.12.004
Abstract

Background: Crude extract of breadfruit has been reported to have antitumor activity against various Cancer cell lines with unknown mechanism.

Purpose: This study aims to investigate the proapoptotic effect of cyclocommunol (CYC), a prenylflavonoid from breadfruit, in two oral squamous cell carcinoma (OSCC) cell lines, SCC2095 and Ca922.

Methods: The antiproliferative effects of CYC were assessed by MTT assays and PI/annexin V analysis. SCC2095 cells were transiently transfected with Mcl-1 plasmid in overexpression experiment. Other methods used to investigate the mechanism of CYC included Western blotting, acridine orange staining and confocal microscopic visualization.

Results: Our results showed that CYC suppressed the viability of SCC2095 and Ca922 with IC50 values at 48 h of 4.2 and 5.0 µM, respectively. This decrease in viability occurred in a caspase-dependent apoptotic manner. In addition, CYC down-regulated the phosphorylation/expression of Akt/mTOR and Mcl-1, accompanied by Reactive Oxygen Species generation, and Autophagy induction. Notably, overexpression of Mcl-1 using Mcl-1-tag-myc partially rescued CYC-mediated Caspase-3 activation, PARP cleavage, and cytotoxicity. In summary, our study demonstrated the proapoptotic activity of CYC on OSCC, partially through down-regulation of Mcl-1.

Conclusion: CYC from breadfruit has translational value as a proapoptotic agent for OSCC.

Keywords

Apoptosis; Autophagy; Breadfruit; Cyclocommunol; Mcl-1; Oral cancer.

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