Inhibition of human glutathione transferase by catechin and gossypol: comparative structural analysis by kinetic properties, molecular docking and their efficacy on the viability of human MCF-7 cells.

Glutathione transferase Pi (GSTP1) expression is increased in many cancer types and is associated with multidrug resistance and apoptosis inhibition. Inhibitors of GSTP1-1 have the potential to overcome drug resistance and improve chemotherapy efficacy as adjuvant agents. This study investigated the effects of catechin and gossypol on human glutathione transferase Pi (GSTP1-1) activity and their cytotoxic effects on breast cancer cells (MCF-7) individually and in combination with tamoxifen (TAM). Gossypol effectively inhibited the enzyme with an IC50 value of 40 µM, compared to 200 µM for catechin. Gossypol showed stronger inhibition of GSTP1-1 activity (Ki = 63.3 ± 17.5 µM) compared to catechin (Ki = 220 ± 44 µM). Molecular docking analysis revealed their binding conformations to GSTP1-1, with gossypol binding at the subunit interface in an un-competitive manner and catechin showing mixed non-competitive inhibition. Gossypol had severe cytotoxic effects on both MCF-7 cells and normal BJ1 cells, while catechin had a weak cytotoxic effect on MCF-7 cells only. Combination therapy with TAM resulted in cytotoxicity of 27.3% and 35.2% when combined with catechin and gossypol, respectively. Gossypol showed higher toxicity to MCF-7 cells, but its strong effects on normal cells raised concerns about selectivity and potential side effects.

Evaluation of Phenolic Content Diversity along with Antioxidant/Pro-Oxidant, Glutathione Transferase Inhibition, and Cytotoxic Potential of Selected Commonly Used Plants.

The function of antioxidant polyphenols has been demonstrated for their ability to protect against a variety of diseases. However, some antioxidants have been shown to be pro-oxidant. Some of the important antioxidant enzymes are glutathione transferases (GST), which are involved in maintaining redox homeostasis. GST class Pi (GSTP1-1) hyper-activation is a feature that is found in cancer. This work aims to demonstrate the relationship between the phytochemicals of 18 plants and their ability to act as antioxidant/pro-oxidant agents, as well as their effects on the activity of GSTP1-1 and their cellular toxicity. Tamarindus indica, Cinnamomum verum, and Alpinia galanga extracts had high phytochemical contents, moderate heavy metal levels, and antioxidant/pro-oxidant activities. Among the main plant components identified using high-performance liquid chromatography, only chlorogenic acid, catechin, and quercetin can function as antioxidants and pro-oxidants. Hibiscus sabdariffa, C. verum, A. galanga, T. indica, Gossypium arboreum, and Punica granatum were among the plant extracts examined that inhibited the activity of the purified recombinant GSTP1-1, with the inhibition constant values ranging from 0.48 to 1.67 mg of gallic acid equivalent/g. The level of cytotoxicity was also studied to determine the effects of these extracts on human Caucasian breast cancer. The findings revealed that plants with high phenol content had an antioxidant/pro-oxidant capacity as well as inhibition of the activity of GST. However, the cytotoxic effect was not associated with all of the extracts, which indicates that polyphenols interact with other components that may influence their observed behavior.