Potential of Melittin to induce apoptosis and overcome multidrug resistance in human colon cancer cell line

Abstract

In this study, the anticancer effect of Melittin was demonstrated through its antiproliferative and proapoptotic effects on HT-29 cells, as well as its ability to reverse multidrug resistance. Melittin directly affects the death receptor-dependent apoptotic pathway via increase of the Fas receptor protein expression, Caspase 8 gene expression and activity of Caspase 8. Results of decreased Caspase 9 gene and protein expression, and multi-fold increased expression of Bcl-2 gene suggest that mitochondria and the inner apoptotic pathway are not involved in the execution of Melittin induced apoptosis, as well as redox regulation of apoptosis based on decreased concentration of superoxide anion radicals and no effect glutathione levels. Specially significance of this work are results on ability of Melittin to modulate the metabolism and export system in cancer cells. Based on the increased expression of all the investigated genes related to the biotransformation process, it can be assumed that CYP1A1, CYP1B1, GSTP1 and MRP2 are involved in metabolism of Melittin in HT-29 cells. P-glycoprotein is associated with the occurrence of resistance in anticancer therapy, so its reduced gene and protein expression by Melittin represents significant result in terms of possible therapeutic application and examination.