Cytotoxic and apoptogenic activity of Bryonia aspera extract on pre-B acute lymphoblastic leukemia cell lines

Abstract

Background: The natural products and conventional chemotherapeutic drug combinations are believed to increase cure rates of anticancer treatment while reducing its toxicity. The current study investigates cytotoxic and apoptogenic effects of methanolic extract of Beryonia aspera, and also synergistic effects of this extract and Prednisolone on acute lymphoblastic leukemia cell lines. Materials and Methods: The under study populations were NALM-6 and REH cell lines. Cells were treated by Prednisolone and B. aspera extract alone and in combination. The effect of the drugs on survival and apoptosis were examined using MTT and flow cytometry, respectively. Moreover, the effects of the drugs on the mRNA expression levels of Bax and Bcl-2 were studied using RQ-PCR. Finally, both the transcriptional and enzymatic activity of caspase-3 were investigated by caspase-3 assay kit. Results: The B. aspera extract induced cell growth inhibition and triggered apoptosis in a dose- and time-dependent manner. Real-time PCR analysis of apoptotic target genes revealed that this agent shifted the ratio of the death promoter to death repressor genes via alteration of Bax and Bcl-2 expression levels. These changes resulted in caspase-3 activation, which led to DNA fragmentation and subsequent apoptosis. Our study has also demonstrated that the combined treatment of B. aspera extract with Prednisolone did not induce greater cytotoxic effect as compared to treatment series using either Prednisolone alone. Conclusion: Our study demonstrated that the B. aspera extract has anti-leukemic properties on BCP-ALL cell lines and could be regarded as a promising agent for the treatment of ALL.

Keywords

• Acute lymphoblastic leukemia
• Bryonia aspera
• Prednisolone
• Apoptosis
• Combination therapy