Rashmi Mallya1,2, Milind J Bhitre2. 1. SVKM's Dr. Bhanuben Nanavati College of Pharmacy, Mumbai, Maharashtra, India. 2. C. U. Shah College of Pharmacy, SNDT Women's University, Mumbai, Maharashtra, India.
Abstract
BACKGROUND: Newer drugs are in demand for leukemia treatment that specifically targets tumor cells without affecting normal cells. Potent cytotoxic activities have been reported from various parts of Zanthoxylum rhetsa. Thus, the present study was conducted to evaluate antileukemic potential of leaf extract of Z. rhetsa along with probable mechanism of cytotoxicity. Materials and Methods: The antiproliferative activity of the extract on leukemic cell lines was evaluated using sulforhodamine B assay. The changes in cell death profile, cell cycle, and expression levels of pro-apoptotic markers (p53, Bax, cytochrome C, caspase 3, and MMP) and antiapoptic marker (Bcl2) on Jurkat cell lines were studied using flow cytometer. Comparison of oxidative stress induced by extract on Jurkat cells and normal mouse fibroblast cells was done. DNA fragmentation was studied using gel electrophoresis. Results: The leaf extract showed concentration-dependent cytotoxicity against Jurkat cell lines majorly via apoptotic mechanism. It arrested cells at G0/G1 and S phase of cell cycle. Apoptosis was associated with increase in the expression of pro-apoptotic markers and decrease of anti-apoptotic markers. The treatment with extract selectively increased the oxidative stress in Jurkat cells and showed DNA fragmentation. Conclusion: The methanol extract of leaves of Z. rhetsa show selective cytotoxic activity on Jurkat cell lines and induced apoptosis via intrinsic pathway.
BACKGROUND: Newer drugs are in demand for leukemia treatment that specifically targets tumor cells without affecting normal cells. Potent cytotoxic activities have been reported from various parts of Zanthoxylum rhetsa. Thus, the present study was conducted to evaluate antileukemic potential of leaf extract of Z. rhetsa along with probable mechanism of cytotoxicity. Materials and Methods: The antiproliferative activity of the extract on leukemic cell lines was evaluated using sulforhodamine B assay. The changes in cell death profile, cell cycle, and expression levels of pro-apoptotic markers (p53, Bax, cytochrome C, caspase 3, and MMP) and antiapoptic marker (Bcl2) on Jurkat cell lines were studied using flow cytometer. Comparison of oxidative stress induced by extract on Jurkat cells and normal mouse fibroblast cells was done. DNA fragmentation was studied using gel electrophoresis. Results: The leaf extract showed concentration-dependent cytotoxicity against Jurkat cell lines majorly via apoptotic mechanism. It arrested cells at G0/G1 and S phase of cell cycle. Apoptosis was associated with increase in the expression of pro-apoptotic markers and decrease of anti-apoptotic markers. The treatment with extract selectively increased the oxidative stress in Jurkat cells and showed DNA fragmentation. Conclusion: The methanol extract of leaves of Z. rhetsa show selective cytotoxic activity on Jurkat cell lines and induced apoptosis via intrinsic pathway.