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.

中文翻译：

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Cyclocommunol通过Mcl-1依赖性机制部分诱导人口腔鳞状细胞癌的凋亡

背景

据报道，面包果粗提取物对各种癌细胞具有未知的机制具有抗肿瘤活性。

目的

这项研究旨在研究环果酚（CYC）（一种来自面包果的异戊二烯类黄酮）在两种口腔鳞状细胞癌（OSCC）细胞系SCC2095和Ca922中的促凋亡作用。

方法

CYC的抗增殖作用通过MTT分析和PI / annexin V分析进行评估。在过量表达实验中，用Mcl-1质粒瞬时转染SCC2095细胞。用于研究CYC机理的其他方法包括Western印迹，a啶橙染色和共聚焦显微镜观察。

结果

我们的结果表明，CYC抑制了SCC2095和Ca922的存活，其48小时的IC ₅₀值分别为4.2和5.0 µM。活力的这种降低以胱天蛋白酶依赖性凋亡的方式发生。此外，CYC下调了Akt / mTOR和Mcl-1的磷酸化/表达，并伴有活性氧的产生和自噬的诱导。值得注意的是，使用Mcl-1-tag-myc过度表达Mcl-1可以部分挽救CYC介导的caspase-3活化，PARP裂解和细胞毒性。总之，我们的研究证明了CYC对OSCC的促凋亡活性，部分是通过下调Mcl-1来实现的。

结论

面包果中的CYC作为OSCC的促凋亡剂具有翻译价值。