Icaritin induces mitochondrial apoptosis by up-regulating miR-124 in human oral squamous cell carcinoma cells.

AIM OF THE STUDY

The present study is aimed to investigate the apoptosis-inducing effect of icaritin in human oral squamous cell carcinoma (OSCC) cells and the associated mechanisms.

MATERIALS AND METHODS

KB and SCC9 cell lines were used as model cell lines. Effect of icaritin on apoptosis was analyzed by flow cytometry. The effect of icaritin on mitochondrial apoptotic pathway was demonstrated by loss of mitochondrial membrane potential and release of cytocrome C from mitochondria. MiR-124 mimic and miR-124 inhibitor were used to manipulate the expression of miR-124 in OSCC cells. SiRNA targeting Sp1 and DNMT1 as well as Sp1 and DNMT1 overexpressing vector were utilized to confirm their roles in the apoptosis-inducing effect of icaritin in OSCC cells. Activation of relevant signaling pathway by icaritin and effect of icaritin on expression of targeting molecules were determined by western blots or qRT-PCR.

RESULTS

Our results showed that icaritin inhibited tumor cell viability in a dose- and time-dependent manner, and induced cell apoptosis via intrinsic mitochondrial pathway by upregulating miR-124. Moreover, our results showed that the icaritin exerted regulatory effect on miR-124 through suppressing Sp1/DNMT1 signaling.

CONCLUSION

Our data provide the first experimental evidence that icaritin induces mitochondrial apoptosis in OSCC cells by upregulating miR-124 and suggest a new mechanism to explain its anti-tumor effects.