Novel drug amooranin induces apoptosis through caspase activity in human breast carcinoma cell lines.
Amooranin (AMR) is a triterpene acid isolated from the stem bark of a tropical tree (Amoora rohituka) grown wild in India. A. rohituka stem bark is one of the components of a medicinal preparation used in the Indian Ayurvedic system of medicine for the treatment of human malignancies. We investigated the mechanism of cell death associated with AMR cytotoxicity in human mammary carcinoma MCF-7, multidrug resistant breast carcinoma MCF-7/TH and breast epithelial MCF-10A cell lines. AMR IC50 values ranged between 3.8-6.9 microg/ml among MCF-7, MCF-7/TH and MCF-10A cells. AMR induced oligonucleosome-sized DNA ladder formation characteristic of apoptosis when tumor cells were treated with 1-8 microg/ml AMR for 48 h. In situ cell death detection assay indicated that AMR caused 37.3-72.1% apoptotic cells in MCF-7, 32-48.7% in MCF-7/TH and 0-37.1% in MCF- 10A cells at 1-8 microg/ml concentrations. The induction of apoptosis in AMR treated cells was accompanied by the elevation of total caspase and caspase-8 activities. Flow cytometric analysis showed that AMR induced caspase-8 activation in 40.8-71% MCF-7, 28.5-43.2% MCF-7/TH and 4-32.8% MCF-10A cells at 1-8 microg/ml concentrations. Our results suggest that AMR is a novel drug having potential for clinical development against human malignancies.
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010936:Plant Extracts; D014315:Triterpenes; C453733:amooranin; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases