Comparison of cytotoxicity and genotoxicity of 4-hydroxytamoxifen in combination with Tualang honey in MCF-7 and MCF-10A cells

Nik Soriani Yaacob,Nur Faezah Ismail

doi:10.1186/1472-6882-14-106

Nik Soriani Yaacob, Nur Faezah Ismail

Open Access

https://doi.org/10.1186/1472-6882-14-106

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Abstract

BackgroundThe Malaysian Tualang honey (TH) is not only cytotoxic to human breast cancer cell lines but it has recently been reported to promote the anticancer activity induced by tamoxifen in MCF-7 and MDA-MB-231 cells suggesting its potential as an adjuvant for the chemotherapeutic agent. However, tamoxifen produces adverse effects that could be due to its ability to induce cellular DNA damage. Therefore, the study is undertaken to determine the possible modulation of the activity of 4-hydroxytamoxifen (OHT), an active metabolite of tamoxifen, by TH in non-cancerous epithelial cell line, MCF-10A, in comparison with MCF-7 cells.MethodsMCF-7 and MCF-10A cells were treated with TH, OHT or the combination of both and cytotoxicity and antiproliferative activity were determined using LDH and MTT assays, respectively. The effect on cellular DNA integrity was analysed by comet assay and the expression of DNA repair enzymes was determined by Western blotting.ResultsOHT exposure was cytotoxic to both cell lines whereas TH was cytotoxic to MCF-7 cells only. TH also significantly decreased the cytotoxic effect of OHT in MCF-10A but not in MCF-7 cells. TH induced proliferation of MCF10A cells but OHT caused growth inhibition that was abrogated by the concomitant treatment with TH. While TH enhanced the OHT-induced DNA damage in the cancer cells, it dampened the genotoxic effect of OHT in the non-cancerous cells. This was supported by the increased expression of DNA repair proteins, Ku70 and Ku80, in MCF-10A cells by TH.ConclusionThe findings indicate that TH could afford protection of non-cancerous cells from the toxic effects of tamoxifen by increasing the efficiency of DNA repair mechanism in these cells.

Highlights

The Malaysian Tualang honey (TH) is cytotoxic to human breast cancer cell lines but it has recently been reported to promote the anticancer activity induced by tamoxifen in MCF-7 and MDA-MB-231 cells suggesting its potential as an adjuvant for the chemotherapeutic agent
We have recently shown that TH could inhibit growth of breast cancer cells, MCF-7 and MDA-MB-231, by inducing apoptosis [16] and promoted the anticancer effects of tamoxifen on these cells [17]
7,12-dimethylbenz [a] anthracene (DMBA)-induced breast tumours in TH-treated rats were reported to be much less in number, volume and weight with better histological grade and morphology compared to the non-honey treated rats [19]

Summary

Introduction

The Malaysian Tualang honey (TH) is cytotoxic to human breast cancer cell lines but it has recently been reported to promote the anticancer activity induced by tamoxifen in MCF-7 and MDA-MB-231 cells suggesting its potential as an adjuvant for the chemotherapeutic agent. Breast cancer patients present with intrinsic resistance to tamoxifen treatment [3] and increasing the dose will only lead to the problem of undesirable effects to the patients as a result of the drug action on normal tissues and cells. These include endometrial cancer risk [4], risk of liver cancers [5] and effect on eyesight [6]. Tamoxifen undergoes metabolic reactions involving the cytochrome P450 enzyme family and lack of this enzyme family was suggested to lead to tamoxifen resistance of the cancer cells [10]

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