Background: The multidrug resistance (MDR) of cancer cells is a major obstacle to cancer treatment. Glutathione S-transferase Pi (GSTP1-1) catalyzes the conjugation of glutathione with anticancer drugs and therefore reduces their efficacy. Phenolic compounds have the potential to inhibit GST P1-1 activity, which is a promising goal to overcome MDR and increase the efficacy of chemotherapy.
Results: Three fractions (dichloromethane, ethyl acetate, and n-butanol) were prepared from Tamarindus indica seeds to determine their phenolic and flavonoid properties as well as their antioxidant/pro-oxidant properties. The n-butanol fraction displayed the highest levels of phenol ( 378 ± 11.7 mg gallic acid equivalent/g DW) and flavonoids (83 ± 6.0 mg rutin equivalent/g DW). Inhibiting effects on purified GSTP1-1 activity in human erythrocytes (eGST), placenta (pGST), and hGSTP1-1 have been studied. The n-butanol fraction was the most effective in inhibiting eGST, hGSTP1-1, and pGST with IC50 values of 3.0 ± 0.7, 4.85 ± 0.35, and 6.6 ± 1.2 μg/ml, respectively. Cellular toxicity was investigated for the T. indica n-butanol fraction on various human cancerous cell lines. The only ones affected were MCF-7 cell lines (72%) and HePG2 (52%) indicated cytotoxicity. The value of IC50 is 68.5 μg/ml of T. indica n-butanol fraction was observed compared to 1.7 μg/ml tamoxifen in MCF-7 cell lines. The combination of treatment of T. indica extract with the medicinally approved drug tamoxifen had unexpected effects; complete elimination of the cytotoxic inhibition effect of tamoxifen and the plant extract was observed.
Conclusions: However T. indica extract has a cytotoxic effect on the MCF-7 cell line; in certain situations, plant products can have an opposite effect to the intended drug, which decreases the impact of the drug.
Keywords: Anticancer drugs; Antioxidant/pro-oxidant balance; Cancer; Glutathione transferase; Herb-drug interaction; Phenolic compounds.