Effects of Apis Dorsata Honey on The Expression of Selected Cyp450, Pro-Apoptotic, and Anti-Apoptotic Genes During Induced Cytotoxicity in Cyclophosphamide-Treated Human Lung Carcinoma (A549) Cells

Abstract

Cyclophosphamide (CP) is a widely used antineoplastic drug used in chemotherapy. Its metabolic activation is mediated by the cytochrome P450 (CYP450) system, a large group of enzymes that are principally found in hepatocytes. In this study, the effect of A. dorsata honey on the expression of selected CYP450 genes, as well as the proapoptotic gene CASP8 and antiapoptotic gene BCL2 was investigated in CP-treated A549 cells using RTqPCR. MTT assay revealed that honey in the lowest concentration (0.6% v/v) most effectively enhanced the cytotoxic effect of CP. Subsequently, gene expression analysis of CYP2J2 and CYP1B1 indicated a 2.38-fold and 1.49-fold upregulation respectively as compared to untreated cells. This suggests that cytotoxicity in A549 cells is favored due to CYP2J2 being relatively more upregulated than CYP1B1. This cytotoxic effect is further enhanced by a 1.65-fold upregulation of the proapoptotic gene CASP8 that is paralleled by a downregulation of the antiapoptotic gene BCL2. Phytosphingosine and sphinganine are notable honey constituents that may be linked to the increased cytotoxicity of CP observed in A549 cells due to their role in promoting apoptosis. The findings in the present study provides further knowledge on the molecular basis by which A. dorsata honey potentiates the cytotoxic effect of cyclophosphamide in A549 cells.