p53-Dependent and p53-Independent Mechanisms of Maerua angolensisInduced Apoptosis in Human Adenocarcinoma Cells: Implications for Broad-Spectrum Cancer Therapy

Abstract Background & Objective: TP53 mutations impair therapeutic responses in ~50% of human cancers, limiting conventional chemotherapy. This study evaluated the apoptosis-inducing mechanisms of Maerua angolensis methanolic leaf extract in p53 wild-type (MCF-7) and p53-mutant (HT-29) cancer cells. Methods: Cytotoxicity (MTT), cell cycle analysis (flow cytometry), gene expression (RT-qPCR), and apoptosis assays (Annexin V/PI) were performed. Results: The extract exhibited moderate cytotoxicity within the biologically relevant range for natural product extracts (IC₅₀ 15.6 μg/mL in MCF-7; 34.4 μg/mL in HT-29). Doxorubicin (IC₅₀ 1.0 μg/mL) and capecitabine (IC₅₀ 10.0 μg/mL) demonstrated higher single-target potency, being 15.6-fold and 3.4-fold more potent than the extract, respectively. In MCF-7 cells, it activated p53-dependent apoptosis via p53↑ (4.2-fold), BAX↑ (3.8-fold), BCL2↓ (0.45-fold), and G0/G1 arrest. In HT-29 cells, it induced p53-independent apoptosis via BAX↑ (2.1-fold), BCL2↓ (0.62-fold), and dual G0/G1 & G2/M arrest. Apoptosis reached >42% in both cell lines. Conclusion: M. angolensis extract induces Apoptosis through both p53-dependent and independent pathways, demonstrating broad-spectrum efficacy with moderate cytotoxicity accompanied by multi-mechanistic activity. Its ability to exploit compensatory apoptotic mechanisms in both p53 wild-type and p53-mutant cells positions it as a promising candidate for complementary cancer therapy, particularly for treating p53-mutant cancers where conventional agents often fail.