Abstract
Herceptin is considered an essential treatment option for double negative breast cancer. Resveratrol and didox are known chemopreventive agents with potential anticancer properties. The aim of the current study is to investigate the influence of resveratrol and didox on the cytotoxicity profile of herceptin in HER-2 receptor positive and HER-2 receptor negative breast cancer cell lines (T47D and MCF-7 cell lines, respectively). The IC50’s of herceptin in T47D and MCF-7 were 0.133 ± 0.005 ng/ml and 23.3795 ± 1.99 ng/ml respectively. Equitoxic combination of herceptin with resveratrol or didox in T47D significantly reduced the IC50 to 0.052 ± 0.001 and 0.0365 ± 0.001 ng/ml, respectively and similar results were obtained in MCF-7. The gene expression of BCL-xl was markedly decreased in T47D cells following treatment with herceptin/resveratrol compared to herceptin alone. Immunocytochemical staining of HER-2 receptor in T47D cells showed a significant reduction after treatment with herceptin/resveratrol combination compared to herceptin alone. On the contrary, herceptin/didox combination had no significant effect on HER-2 receptor expression. Cell cycle analysis showed an arrest at G2/M phase for both cell lines following all treatments. In conclusion, herceptin/resveratrol and herceptin/didox combinations improved the cytotoxic profile of herceptin in both T47D and MCF-7 breast cancer cell lines.
Highlights
We investigated the potential chemo-modulatory effects of resveratrol and didox to herceptin against HER-2 positive and negative breast cancer cell lines
To study the effect of resveratrol and didox on the cytotoxic profile of herceptin, the dose response curve of herceptin alone was assessed relative to its combination with resveratrol or didox in two different breast cancer cell lines; MCF-7 and T47D (Table 1)
In the current study the combinations of resveratrol and didox with herceptin were tested in two breast cancer cell lines; T47D ( HER-2 + ve) and MCF-7 ( HER-2 − ve)
Summary
The values of the IC50’s of DID are deduced from the equitoxic ratios of HER/DID in T47D (1/1000) and in MCF-7 (1/200).Multiple comparisons were achieved using one way analysis of variance (ANOVA) followed by LSD post hoc test. Herceptin (trastuzumab) is a recombinant humanized anti-HER-2 monoclonal antibody approved for the treatment of HER-2 overexpressing metastatic breast cancer. Resveratrol has been shown to exhibit several potential chemoprotective activities in cell and animal models, including inhibition of PI3K/AKT pathway[13]. Didox has shown several chemomodulatory effect to several classic and non-classic anticancer agents such as doxorubicin liver cancer cells, melphalan in multiple myeloma, and cidofovir in nasopharyngeal carcinomas. Didox enhanced the anticancer properties of doxorubicin against liver cancer cells and protected from its dose limiting cardiotoxicity[16]
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