DNA Damage Underlies the Cytotoxic and Apoptotic Effects of Selected Ethiopian Medicinal Plants against Cancer Cell Lines

Background: Plants are attractive sources of anti-cancer agents. However, there is limited data about the anti-cancer potential of Ethiopian medicinal plants traditionally used for the treatment of cancer. Objectives: To screen the cytotoxicity of 26 Ethiopian medicinal plants against breast cancer cells (MCF-7) and to demonstrate the potential consistent cytotoxicity of the six most active extracts against prostate cancer cell line (PC-3) and neuroblastoma (SH-SY5Y). Furthermore, the mode of action of the most active extracts should be investigated. Materials and Methods: Twenty-six Ethiopian medicinal plants were collected from 12 sites and extracted using 80% methanol through maceration. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to test their cytotoxicity. Annexin V/propidium iodide (PI) assay was used to segregate the type of death induced by the extracts. The Western Blot was used to analyze deoxyribonucleic acid (DNA) damaging properties of active extracts, while chromatographic techniques [thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC)] were employed to provide a fingerprint of the most active extract. Results: Dovyalis abyssinica (A. Rich.) Warb. extract displayed the most potent cytotoxic activity against MCF-7 and SH-SY5Y cells with the half-maximal inhibitory concentration (IC50) values of 28.28 ± 3.56 and 5.5 ± 3.9 µg/mL, respectively. It also increased apoptotic cell populations from 0.05% to 12.4%, 0.9% to 14.4%, and 1.8% to 64.5% (p < 0.0001 in all cases) in MCF-7, SH-SY5Y, and PC-3 cells. Acokanthera schimperi Benth. & Hook.f., D. abyssinica, Erythrina brucei Schweinf., Pittosporum abyssinicum Delile, Rubia cordifolia L., and Stephania abyssinica var. tomentella Oliv. significantly (p < 0.0001) elevated the expression of phosphohistone H2AX (γH2AX) in at least one cancer cell line. Poly-ADP-ribose polymerase-1 (PARP-1) also significantly increased (p < 0.0001) by D. abyssinica and R. cordifolia in MCF-7 cells. Conclusion: Some Ethiopian medicinal plant extracts showed marked cytotoxicity against MCF-7, PC-3, and SH-SY5Y cancer cell lines, promoting apoptosis through DNA damage and encouraging phytochemical investigations for potential drug development.