Antioxidant or pro-oxidant and glutathione transferase P1-1 inhibiting activities for Tamarindus indica seeds and their cytotoxic effect on MCF-7 cancer cell line

R.A Guneidy,A.M Gad,E.R Zaki,F.M Ibrahim,A Shokeer

doi:10.1186/s43141-020-00077-z

R.A Guneidy, A.M Gad + Show 3 more

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https://doi.org/10.1186/s43141-020-00077-z

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Abstract

BackgroundThe 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. ResultsThree 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. ConclusionsHowever 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.

Highlights

The multidrug resistance (MDR) of cancer cells is a major obstacle to cancer treatment
The IC50 values using DPPH scavenging activity showed that n-butanol fraction of T. indica seeds has a powerful antioxidant capacity ( 2.1± 0.08 mg/g dry weights (DW), p < 0.001) followed by the ethyl acetate fraction (45 ± 3 mg/g DW) and the dichloromethane fraction (165 ± 11 mg/g DW)
The use of the plant extract (T.indica) with the medicinally approved drug has contributed to the complete cancelation of the effect of the drug and to the cancelation of the effect of the herbal extract, which has been shown to be effective in killing cancer cells as shown in the results, indicated the following:

Summary

Introduction

The multidrug resistance (MDR) of cancer cells is a major obstacle to cancer treatment. Due Multidrug resistance (MDR) for cancer cells limits the therapeutic effect of anticancer drugs and is a major barrier to cancer treatment. GST catalyzes the conjugation of GSH with anticancer drugs to prevent direct drug activity; this conjugation reduces the ability of anticancer drugs to penetrate the cell and to attack cellular DNA [4]. This activity appears to occur preferably via isoform (GSTP1-1); GSTP interacts with a number of small molecules and cellular proteins that produce regulatory effects across the main signaling and transcription pathways (identified as the “GSTP regulatory interactome”). Inhibiting GST activity can inhibit the function of the C-Jun N-terminal kinase (JNK) signal regulator and improving cell signaling pathways in cancer cells and apoptosis [5, 6]

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