Antiproliferative Activities, Gene Expression Profiles and Toxicity of Selected Medicinal Plants against Cancerous and Normal Cells

Abstract

Cancer is among the leading causes of morbidity and mortality worldwide and accounts for up to 28,000 deaths annually in Kenya. Globally, approximately 13% of all deaths annually are attributed to cancer. Surgery, radiation and chemotherapy are the current treatment techniques for cancer; however, these methods are expensive, have high failure rates and have been associated with detrimental side effects. Plants derived products could be good candidates in alleviating challenges being experienced with current methods. This study aimed at evaluating the phytochemistry, antiproliferative potential, safety and probable mechanism of action of Albizia gummifera, Senna didymobotrya, and Rhamnus staddo extracts. Preliminary phytochemical screening was done as per standard procedures. The common 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium (MTT) dye was used in the determination of the antiproliferative activity of the extracts. Extracts induction of VEGF (angiogenesis) and p53 (apoptosis) genes’ expression was evaluated using Real Time Polymerase Chain Reaction with GAPDH as the endogenous control. Acute oral and sub-acute toxicity was evaluated in female Albino Swiss mice. Phytochemical screening revealed presence of alkaloids, tannins, glycosides, flavonoids, terpenes, phenolics and saponins in the plants extracts. A. gummifera’s stem bark methanol: dichloromethane extract had the highest activity against the cancerous cell lines tested viz: HCC1395 (IC50 6.07±0.04μg/ml), DU145 (IC50 3.34±0.05μg/ml), CT26 (IC50 5.78±0.08μg/ml) and Hep2 (IC50 7.02±0.01μg/ml). R. staddo root bark methanol: dichloromethane extract had an IC50 value of 15.71±0.04μg/ml on HCC, 9.81±0.09μg/ml on Hep2 and 11.14±0.39μg/ml on CT26. S. didymobotrya root bark methanol: dichloromethane extract inhibited HCC with an IC50 65.06±0.07μg/ml, CT26 with an IC50 15.71±0.04μg/ml and Hep 2 with an IC50 62.10±0.11μg/ml. From the results obtained, the plants exhibited selective inhibition to cancer cells while sparing the normal cells (SI ≥ 3). A. gummifera, S. didymobotrya and R. staddo plant extracts upregulated p53 and down-regulated VEGF gene. For the acute toxicity, no mortality and no significant changes were observed in body weight and wellness parameters at 50, 300 and 2000mg/kg body weight doses of the plants’ extracts. The sub-acute toxicity, however, demonstrated toxic effects as evidenced by the hematological and biochemical parameters changes, weekly change in body weights, changes in organ weights and relative organ to body weights of mice. In conclusion, this study confirms potential application of these plants in cancer management and act as a lead to cancer drug development. The phytochemicals present in these plants are most possibly responsible for the antiproliferative and potential anticancer activities.