Abstract
The total alkaloid extract from Prosopis juliflora DC. leaves was obtained using acid/base modified extraction method. The in vitro anti-tumor potential of the extract was evaluated using MTT (3-(4,5-dimethythiazol-2yl)2,5-diphenyl tetrazolium bromide) based cytotoxicity monitoring after 24, 48 and 72 h exposure of the MOLT-4 cells (1×106 cells/ml medium) to different concentration of the extract ranging from 10 to 100 µg/ml medium. The genotoxic potential of the extract was also tested using cytokinesis block in vitro micronucleus assay. Simultaneously, the cytotoxic and genotoxic potential of the extract were compared with mitogen stimulated T-lymphocyte cultures derived from peripheral blood of healthy volunteers. The MTT test revealed that, the extract exhibited comparatively higher toxicity towards the cancer cells than the normal cells at all the tested concentrations and at all the time points studied. The IC50 values of the extract at 24, 48 and 72 h were found to be 90.5, 42.5 and 20.0 µg/ml/1× 106 cells against cancer cells. The genotoxic assay showed that, in both cultures, the number of micronuclei obtained even at the highest exposure concentration tested was very low when compared with that of the micronuclei obtained with the positive control mitomycin-C. The results of the present investigation demonstrate that, P. julifloraleaf alkaloids are preferentially cytotoxic to human T-cell leukemia (Molt-4) cells in a dose and time dependent manner with the absence of genotoxicity. Key words: Prospis juliflora, alkaloids, molt-4 cells, MTT test, micronucleus assay.
Highlights
Cancer is the second leading cause of death in the world (Madhusudan and Middleton, 2005)
When the same extracts were exposed to normal cells for the same duration at similar concentration, determination of IC50 values to normal cells was not possible at all the time points studied which showed that, the growth inhibition by TAE was significantly lesser in normal cells than in cancer cells
The cytotoxicity observed in cancer cells at the highest exposure concentration (100 μg/ml medium) was found to be 53.86, 66.74 and 72.65% after 24, 48 and 72 h incubition, where as, the same for normal cells was found to be 29.24, 38.37 and 46.51%, respectively for the same durations
Summary
Cancer is the second leading cause of death in the world (Madhusudan and Middleton, 2005). Over 60% of the drugs are derived in one or the other way from natural sources including plant, marine organisms and micro-organisms (Newman et al, 2003). Among many recent advances in cancer chemotherapy, plant natural products have played an important role in contributing to approximately 60 cancer chemotherapeutic drugs on the market including Catharanthus (Vinca) alkaloids (vinblastine, vincristine, vinorelbine), the pipodophyllotoxins. (etoposide, etoposide phosphate, teniposide), the taxanes (paclitaxel and docetaxel) and the camptothecin derivatives (irinotecan and topotecan) (Cragg et al, 1997; Kinghorn, 2000; Conforti et al, 2008; Dholwani et al, 2008; Bhuvan et al, 2009). In large number of medicinal plants, the therapeutic value is due to the presence of alkaloids, which in certain respects, ranks among the most interesting of the naturally occurring substances (Ahmad et al, 1995).
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