Dual Action of Resveratrol: Inhibition of Human Glutathione Transferase and its Antagonism with Tamoxifen on Breast Cancer Cell Viability | ||
| Egyptian Journal of Chemistry | ||
| Volume 67, Issue 12, December 2024, Pages 601-611 PDF (2.18 M) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/ejchem.2024.325338.10562 | ||
| Authors | ||
| Abeer Shokeer* 1; Eman R. Zaki2; Nevein Saleh3; Rasha Guneidy4 | ||
| 1Molecular Biology Department, National Research Centre, 23 El Tahrir street, Dokki, Egypt | ||
| 2Molecular Biology Department, National Research Centre , Cairo , Egypt | ||
| 3National Research Centre | ||
| 4There is no funding to publish this research and therefore all authors hope to be relieved of the publishing cost | ||
| Abstract | ||
| It is believed that breast cancer is the second leading cause of death among women. Resveratrol, also known as phytoestrogen, exhibits anti-cancer, anti-oxidant, and anti-inflammatory properties. It is a trans-stilbene and a non-flavonoid polyphenol. This study examined the impact of resveratrol on the activity of human glutathione transferase P1-1 (hGST P1-1) and its efficacy when combined with tamoxifen using MCF-7 breast cancer cells. Steady-state kinetics and molecular docking were demonstrated to show the effect of inhibition of resveratrol on hGST P1-1. Resveratrol acts as a mixed noncompetitive inhibitor for hGST P1-1 by using glutathione (GSH) as a substrate, altering both Vmax and KM. The Ki values were investigated of 71±12.6 µM for GSH, indicating that resveratrol can interact with the free enzyme and the enzyme-substrate complex. Molecular docking studies revealed interactions between both resveratrol and tamoxifen with the hGST P1-1 dimer-interface. The combination of resveratrol and tamoxifen showed antagonist effect on MCF-7 cell viability, suggesting potential complexities and challenges in their combines use for therapeutic purposes. The antagonistic effect suggests that resveratrol could interfere with the therapeutic efficacy of tamoxifen, potentially through molecular mechanisms. This study investigates the importance of understanding drug interactions at molecular level and highlights the necessity for careful consideration when combining therapeutic agents. | ||
| Keywords | ||
| Glutathione transferase P1 inhibition; trans-Resveratrol; Structure-function relationship; Tamoxifen | ||
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