Introduction: Terminalia spp. are characterised by their high levels of antioxidant phytochemicals and several species have anticancer activity. This study examines the anti-proliferative activity of T. sericea leaf extracts against Caco2 and HeLa carcinoma cell proliferation. Methods: Solvent extracts were prepared from T. sericea leaves and their antioxidant capacities were determined by the DPPH free radical scavenging assay. Anti-proliferative activities against Caco2 and HeLa cancer cells were determined by an MTS based cell proliferation assay. Toxicity was determined using the Artemia franciscana nauplii bioassay. Results: The methanolic and aqueous T. sericea leaf extracts displayed high antioxidant capacities (equivalent to 150 and 340 mg of ascorbic acid per gram of plant material extracted respectively). In contrast, the ethyl acetate, chloroform and hexane extracts had relatively low antioxidant contents (≤5 mg of ascorbic acid equivalents per gram of plant material extracted). The antioxidant contents of the T. sericea leaf extracts correlated with the ability of the extracts to inhibit proliferation of Caco2 and HeLa cancer cell lines. The high antioxidant methanolic and aqueous extracts were potent inhibitors of cell proliferation, with IC 50 values 120-1400 µg/mL. The aqueous T. sericea leaf extract was particularly effective, with IC 50 values of 528 and 120 µg/mL against Caco2 and HeLa cells respectively. The methanolic extract also displayed good, albeit substantially less potent, antiproliferative activity against HeLa cells, with an IC 50 of 1358 µg/mL. In contrast, the lower antioxidant content extracts generally did not inhibit cancer cell proliferation. Cell imaging studies detected morphological features consistent with apoptosis in Caco2 cells exposed to sub-lethal concentrations of the methanolic and aqueous T. sericea leaf extracts, indicating that these extracts are functioning by cytotoxic mechanisms. The aqueous T. sericea leaf extract displayed low to moderate toxicity in the Artemia franciscana bioassay, with an LC 50 value of 737 µg/mL. All other extracts were nontoxic. Conclusion: The antiproliferative activity and low toxicity of the T. sericea methanolic and aqueous leaf extracts extracts against HeLa and Caco2 cancer cell lines indicates their potential in the treatment and prevention of some cancers.

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