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Identification of Bioactive Compounds in Warburgia salutaris Leaf Extracts and Their Pro-Apoptotic Effects on MCF-7
Lebogang Valentia Monama1, Daniel Lefa Tswaledi1, Tshisikhawe Masala Hadzhi1
1Department of Biochemistry and Biotechnology, School of Science and Technology, Sefako Makgatho Health Sciences University, Pretoria 0204, South Africa.
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 Warburgia salutaris 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. Warburgia salutaris 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 W. salutaris leaf extracts in the development of anticancer drugs.
Insights
Warburgia salutaris leaf extracts demonstrate anticancer potential by inducing apoptosis in MCF-7 cells. These natural compounds show antiproliferative effects and inhibit metastasis, offering new avenues for drug development.
Area of Science:
- Pharmacology and Natural Products Research
- Cancer Biology and Therapeutics
- Molecular Mechanisms of Cell Death
Background:
- Apoptosis is a critical cellular process, and its dysregulation contributes to cancer development and drug resistance.
- Natural products offer a promising source for novel anticancer agents.
- Warburgia salutaris is a plant with traditional medicinal uses, warranting investigation for its bioactive compounds.
Purpose of the Study:
- To screen volatile compounds from Warburgia salutaris leaf extracts for their potential anticancer activity.
- To investigate the pro-apoptotic effects of these extracts on MCF-7 breast cancer cells.
- To elucidate the underlying molecular mechanisms of action.
Main Methods:
- Cell viability was assessed using MTT and scratch assays.
- DNA synthesis and damage were evaluated with BrdU and comet assays.
- Morphological changes were observed via DAPI/PI staining; protein expression was analyzed by RT-PCR and a human apoptotic proteome profiler.
Main Results:
- Warburgia salutaris extracts exhibited significant time- and dose-dependent antiproliferative effects on MCF-7 cells.
- Acetone and methanol extracts showed low IC50 values, indicating potent cytotoxicity.
- Treatment inhibited MCF-7 cell metastasis and upregulated pro-apoptotic proteins, including Bax and caspase-3, suggesting activation of the intrinsic apoptotic pathway.
Conclusions:
- Warburgia salutaris leaf extracts possess potent antiproliferative and anti-metastatic properties against MCF-7 cells.
- The extracts induce apoptosis predominantly through the intrinsic pathway, evidenced by Bax and caspase-3 upregulation.
- These findings highlight the therapeutic potential of Warburgia salutaris in developing novel anticancer drugs.
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