Identification of Bioactive Compounds in Warburgia salutaris Leaf Extracts and Their Pro-Apoptotic Effects on MCF-7 Breast Cancer Cells

Abstract

The apoptotic mechanism is complex and involves many pathways. Defects can occur at any time along these pathways, resulting in malignant cell transformation and resistance to anticancer drugs. Collective efforts have made great progress in the implementation of natural products in clinical use and in discovering new therapeutic opportunities. This study aimed to screen volatile compounds of <i>Warburgia salutaris</i> leaf extracts and investigate their pro-apoptotic effects on MCF-7 cells. The approach was mainly based on determining cell viability using MTT and scratch assays, and DNA synthesis and damage using BrdU and comet assays, respectively. DAPI/PI stains were used for morphological analysis and expression was determined by RT-PCR and human apoptotic proteome profiler. <i>Warburgia salutaris</i> extracts exhibited antiproliferative effects on MCF-7 cells in a time- and dose-dependent manner. Acetone and methanol extracts exhibited low IC₅₀ at 24, 48 and 72 h. Furthermore, the scratch test revealed that MCF-7 does not metastasise when treated with IC₅₀. Expression showed upregulation of pro-apoptotic proteins and executioner caspases. Taken together, these findings suggest that leaves can promote apoptosis through the intrinsic apoptotic pathway, as observed by upregulation of the Bax and caspase 3 proteins. This paper provides new insights into the mechanisms of action of <i>W. salutaris</i> leaf extracts in the development of anticancer drugs.