Comparison of cytotoxicity and genotoxicity of
4-hydroxytamoxifen in combination with Tualang honey in MCF-7 and MCF-10A cells
BMC Complement Altern Med, 2014 Mar 19;14(1):106
BACKGROUND:
The 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.
METHODS:
MCF-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.
RESULTS:
OHT 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.
CONCLUSION:
The 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.
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