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 IC 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.
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