Aristolochia longa aqueous extract triggers the mitochondrial pathway of apoptosis in BL41 Burkitt’s lymphoma cells

Abstract

Aristolochia longa (from the family Aristolochiaceae) is widely used for cancer treatment in Algerian traditional medicine. The aim of the present study was to investigate the cytotoxic and apoptogenic activities. The phytochemical composition and acute toxicity of aqueous extracts of the roots of A. longa from Algeria. An aqueous extract (decoction) of dried A. longa roots was prepared. The cytotoxic effects of this aqueous extract were then evaluated in Burkitt’s lymphoma BL41 cells, by flow cytometry. The induction of apoptosis was assessed in two corroborative assays: The propidium iodide staining of cell DNA and flow cytometry analyses of light scattering. Mitochondrial membrane potential was investigated with the fluorescent dye DIOC6. The expression and activation of capases-3, -8 and -9 were assessed by Western blotting. Acute oral toxicity was evaluated with a test dose limited to 5000 mg/kg. Phytochemical screening of A. longa roots was performed with standard qualitative procedures. The aqueous extract of A. longa induced cell death in a dose-dependent manner. The IC50 of A. longa aqueous extract was estimated at about 15,63 μg/ml. The extract-induced apoptosis, a loss of mitochondrial membrane potential and the activation of caspases-9 and -3 followed by PARP cleavage. A. longa could therefore be considered a promising source of novel treatments for Burkitt’s and other lymphomas. Key words: Apoptosis, Aristolochia longa, Burkitt’s lymphoma BL41 cell lines, caspase, mitochondrial pathway