Antiproliferative and Apoptotic Activities of the Medicinal Plant Ziziphus obtusifolia

Background: Ziziphus obtusifolia is a spiny shrub found in Northwest Mexico desert, with traditional medicinal use to treat several diseases including cancer. Objective: The aims of the present study were to evaluate the antiproliferative and apoptotic activities of the aerial parts of this plant. Materials and Methods: The methanol extract and its fractions were prepared using several solvents. The antiproliferative activity was evaluated by the (3‑[4,5‑dimethylthiazol‑2‑yl]‑2,5‑diphenyltetrazolium) (MTT) assay on HeLa, A549, RAW 264.7, M12.C3.F6, and L‑929 cell lines, and the apoptotic activity using Annexin V and (5,50,6,60‑tetra‑chloro‑1,10,3,30‑tetra‑ethylbenzimidazol‑carbocyanine iodide) staining. The most active fraction was further separated by column chromatography. Results: The most active fraction was hexane with an IC₅₀ of 90.4 µg/mL against RAW 264.7, 94 µg/mL against M12. C3.F6, 165.5 µg/mL against HeLa and 187.7 µg/mL against A549 cell lines. In apoptotic activity assays the methanol extract and its n‑hexane fraction were found to induce mitochondrial depolarization in HeLa cells (83 and 87% respectively), and both induced the externalization of the phosphatidylserine increasing the percentage of cells in early apoptosis from 1.4% in untreated control cells, to 1.9% and 3.5% for methanol extract and n‑hexane fraction‑treated cells, respectively, statistically different for the total percentage of apoptotic cells (P < 0.05). Conclusions: These results show that Z. obtusifolia has antiproliferative a