Anticancer Activity and Molecular Mechanism of Polyphenol Rich Calophyllum inophyllum Fruit Extract in MCF-7 Breast Cancer Cells

ABSTRACT

This study was conducted to investigate the anticancer effects and mechanism of Calophyllum inophyllum fruit extract against MCF-7 cells. C. inophyllum fruit extract was found to have markedly cytotoxic effect against MCF-7 cells in a dose-dependent manner with the IC₅₀ for 24 h of 23.59 µg/mL. Flow cytometry analysis revealed that C. inophyllum fruit extract mediated cell cycle at G₀/G₁ and G₂/M phases, and MCF-7 cells entered the early phase of apoptosis. The expression of anti-apoptotic proteins Bcl-2 was decreased whereas the expression of the pro-apoptotic protein Bax, cytochrome C and p53 were increased after treatment. C. inophyllum fruit extract led to apoptosis in MCF-7 cells via the mitochondrial pathway in a dose dependent manner. This is evidenced by the elevation of intracellular ROS, the loss of mitochondria membrane potential (Δψm), and activation of caspase-3. Meanwhile, dose-dependent genomic DNA fragmentation was observed after C. inophyllum fruits extract treatment by comet assay. This study shows that C. inophyllum fruits extract-induced apoptosis is primarily p53 dependent and mediated through the activation of caspase-3. C. inophyllum fruit extract could be an excellent source of chemopreventive agent in the treatment of breast cancer and has potential to be explored as green anticancer agent.

Acknowledgments

Shanmugapriya was supported by the MyMSc fellowship from the Ministry of Higher Education, Government of Malaysia, Malaysia.

Conflict of Interest

The authors declare that there are no conflicts ofinterest.