Induction of Apoptosis and Modulation of Caspase Activity on MCF-7 Human Breast Cancer Cells by Bioactive Fractionated Cocoa Leaf Extract

Document Type : Research Articles


1 Department of Nutrition and Dietetics, College of Pharmacy, Al-Ain University, Abu-Dhabi, United Arab Emirates.

2 Faculty of Applied Sciences and Technology, Universiti Tun Hussein Onn Malaysia (UTHM)- Pagoh Campus, Johor, Malaysia.

3 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia.

4 Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Al-Azhar University of Gaza, Gaza City, State of Palestine.

5 Sport and Exercises Sciences School, Faculty of Science, Liverpool John Moores University, Liverpool, UK.


Background: The objective of this study was to investigate the potential anti-proliferative activities of a methanolic extract of cocoa leaves (CL) obtained through sequential partition and fractionation against MCF-7 breast cancer cells.  Methods: The methanolic extract of CL was partitioned in three separated solvents (hexane, dichloromethane, and methanol). Hexane partition was the most potent against MCF-7 cells growth with the lowest IC50 value. Then, it was subjected to two fractionation procedures, resulting in the identification of the CL bioactive fraction (II-F7) with potent toxicity against MCF-7 cells. Results: Further investigation into CL bioactive fraction (II-F7) revealed significant dose-dependent growth inhibitory effects on MCF-7 cells, which were attributed to the induction of apoptosis, as evidenced by the presence of apoptotic bodies, fragmented DNA, and disruption of mitochondrial membrane potential. Additionally, treatment with CL bioactive fraction (II-F7) upregulated the expression of pro-apoptotic genes (DDIT3, GADD45G and HRK) and significantly increased the activities of caspase-8 and caspase-9. Conclusion: Overall, this study suggests that bioactive fraction (II-F7) from CL extract has significant and selective cytotoxicity against MCF-7 cells through inducing apoptosis and has potential as a therapeutic agent for breast cancer treatment.


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