Antitumor activity of 4-O-Methylhonokiol in human oral cancer cells is mediated via ROS generation, disruption of mitochondrial potential, cell cycle arrest and modulation of Bcl-2/Bax proteins.

PURPOSE

The plant-derived natural product 4-O-methylhonokiol (MH) has been reported to possess tremendous pharmacological potential ranging from neuroprotection to anticancer activity. However, the anticancer activity of MH in oral squamous cell carcinoma (OSCC) cells has not been evaluated. In the present study, MH was evaluated for its anticancer activity against OSSC PE/CA-PJ41 cells and the possible underlying mechanism was determined.

METHODS

Cell cytotoxicity was evaluated by colorimetrybased MTT assay while the effects on cell cycle phase distribution were assessed by flow cytometry. Effects of MH on reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) were evaluated by flow cytometry. Western blot assay was finally utilized to study the effects of MH on key cancer and apoptosis-linked proteins including Bax and Bcl-2.

RESULTS

MH induced cytotoxicity in OSCC PE/CA-PJ41 cells with an observed IC50 of 1.25 μM. It also caused significant increase in the production of ROS and disrupted the MMP in a dose-dependent manner. The reduction in MMP favored mitochondrial apoptotic pathway which was further confirmed by determining the expression of Bax and Bcl-2. It was observed that MH downregulated the expression of Bax and upregulated the expression of MMP, ultimately leading to apoptosis of OSSC PE/CA-PJ41 cells. Additionally, MH also caused G2/M cell cycle arrest in a dose-dependent manner.

CONCLUSION

Taken together, our results indicate that 4-Omethylhonokiol may prove a potential natural anticancer molecule against human oral carcinoma cells.