Effect of Apis dorsata honey on cyclophosphamide-induced cytotoxicity and genotoxicity in human lung carcinoma (A549) cells and murine embryonic fibroblast (NIH 3T3) cells

Abstract

The efficiency of chemotherapeutic drugs are limited by their severe adverse effects to non-cancer cells. Natural substances capable of reducing the adverse effects of antineoplastic drugs to normal cells without compromising the drug’s anticancer effect are therefore warranted. The effect of Apis dorsata honey on the in vitro cytotoxicity and genotoxicity of cyclophosphamide (CP) to cancer and normal cells were studied in two cell culture systems using Human Lung Carcinoma (A549) cells and Normal Murine Embryonic Fibroblasts (NIH 3T3). Cytotoxicity resulting from CP and CP+honey treatments were determined using MTT assay whereas genotoxocity was estimated using in vitro micronucleus assay. A. dorsata honey was analyzed using liquid chromatography-mass spectrometry (LC-MS) to detect putative honey active components. It was shown that A. dorsata honey in low concentrations (0.01mg/ml) increased CP-induced cytotoxicity to cancer (A549) cells and at high concentrations (10mg/ml) decreased CP-induced cytotoxicity to normal (NIH 3T3) cells. A. dorsata honey also increased CP sensitivity index from 1 to 1.48. Honey co-treatment significantly reduced micronucleus counts by 56% in 2mg/ml CP-treated NIH 3T3 cells, thereby illustrating its potential as a protective agent against CP-induced genotoxicity. Putative compounds from LC-MS analysis include sucrose, phytosphingosine, 14(15)-EET-sulfonimide, S32826, didrovaltratum, and citranaxanthin. It was shown that A. dorsata honey has a potential in reducing the adverse effects of cyclophosphamide to NIH 3T3 cells while potentiating CP’s effects against A549xiv cells. However, honey’s protective effects were shown to be dependent on honey and cyclophosphamide concentrations.