Effects of Honey on the mRNA Expression of Selected , Pro-apoptotic, and Anti-apoptotic Genes during Induced Cytotoxicity in Cyclophosphamide-treated Human Lung Carcinoma (A549) Cells.

INTRODUCTION

One of the novel strategies in cancer treatment is the combination of conventional chemotherapeutic drugs and natural products. In a previous study, co-treatment of the anti-cancer drug cyclophosphamide (CP) with honey from giant honey bee () resulted to a dose-dependent increase in its cytotoxic effect in human lung carcinoma (A549) cells. However, the molecular mechanism of this combinatorial effect remains unknown.

OBJECTIVES

In this study, the effect of honey on the expression of selected CYP450 genes at the mRNA level, as well as the proapoptotic gene and antiapoptotic gene was investigated in CP-treated A549 cells.

METHODS

MTT Assay was performed to determine the cell viability of A549 cells after treatment with CP with or without honey, as well as the EC of CP with honey thereafter. RT-qPCR was then performed to study the effect of honey on the expression of selected CYP450 genes as well as and genes in CP-treated A549 cells. LC-MS was carried out to screen for putative compounds in honey which may possibly have anti-cancer activity.

RESULTS

Honey in the lowest concentration (0.6% v/v) most effectively enhanced the cytotoxic effect of CP. and indicated a 2.38-fold and 1.49-fold upregulation, respectively as compared to untreated cells. This cytotoxic effect is further enhanced by upregulation of that is paralleled by a downregulation of . Phytosphingosine and sphinganine are honey constituents which may be linked to the increased cytotoxicity of CP observed in A549 cells.

CONCLUSION

This study provides further knowledge on the molecular basis by which honey potentiates the cytotoxic effect of cyclophosphamide in A549 cells.