Preclinical anticancer studies on the ethyl acetate leaf extracts of Datura stramonium and Datura inoxia

Background: Cancer is a horrific disease relentlessly affecting human population round the globe. Genus Datura encompasses numerous species with reported medicinal uses. However, its potential as a source of natural anticancer agents is yet to be determined. Datura stramonium (DS) and Datura inoxia (DI) are the two species chosen for this study. Methods: Total phenolic and flavonoid content (TPC and TFC) as well as antioxidant activity were assessed through colorimetric method. Polyphenolic quantification was done by RP-HPLC. Following extract standardization ethyl acetate leaf extracts of both species (DSL-EA and DIL-EA) were chosen for anticancer studies. In vitro cytotoxicity using various models including cancer cell lines was monitored. Following toxicity studies, benzene (0.2 ml) was used to induce leukemia in Sprague-Dawley rats. Extracts were orally administered to preventive (100 and 200 mg/kg) and treatment (200 mg/kg only) groups. The antileukemic potential of extracts was assessed through haematological, biochemical, endogenous antioxidants and histological parameters. Results: Significant TPC and TFC were estimated in DSL-EA and DIL-EA. RP-HPLC quantified (mu g/mg extract) rutin (0.89 +/- 0.03), gallic acid (0.35 +/- 0.07), catechin (0.24 +/- 0.02) and apigenin (0.29 +/- 0.09) in DSL-EA while rutin (0.036 +/- 0.004) and caffeic acid (0.27 +/- 0.03) in DIL-EA. Both extracts exhibited significant brine shrimp cytotoxicity (LC50 < 12.5 mu g/ml). DIL-EA exhibited greater cytotoxicity against PC-3, MDA-MB 231 and MCF-7 cell lines (IC50 < 3 mu g/ml in each case) as well as higher protein kinase inhibitory action (MIC: 25 mu g/disc) compared to DSL-EA. Leukemia induced in rats was affirmed by elevated serum levels of WBCs (7.78 +/- 0.012 (x 10(3)) / mu l), bilirubin (7.56 +/- 0.97 mg/dl), Thiobarbituric acid reactive substances (TBARs) (133.75 +/- 2.61 nM/min/mg protein), decreased RBCs (4.33 +/- 0.065 (x 10(6))/mu l), platelets (344 +/- 3.19 (x 10(3))/mu l), total proteins (2.14 +/- 0.11 g/dl), Glutathione S-transferases (GST) (81.01 +/- 0.44 nM/min/ml), endogenous antioxidant enzymes levels and abnormal liver and kidney functionality in disease control rats. Both species revealed almost identical and significant (p < 0.05) alleviative effects in benzene induced leukemia. Conclusion: Comprehensive screening divulged the tremendous potential of selected species as potent source of natural anticancer agents in a variety of cancers particularly leukemia. Present study might provide useful finger prints in cancer research and mechanistic studies are prerequisite in logical hunt of this goal.