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Research Article Open access CC BY 4.0

Effect of Methotrexate and Tea Polyphenols on the Viability and Oxidative Stress in MDA-MB-231 Breast Cancer Cells

Theresa Kelly, Richard K. Owusu-Apenten

Journal of Applied Life Sciences International · pp. 152–159 · Published 24 Mar 2015

10.9734/JALSI/2015/14142

Abstract

Aim: To determine the effect of tea polyphenols and methotrexate on viability and reactive oxygen species (ROS) in a naturally resistant breast cancer cell line MDA-MB-231. Methodology: MDA-MB-231 cells were selected as a model for methotrexate resistant breast cancer. Drug tests were performed over 72 hours at concentrations 0-100 µM. Pre-treatments were with quercetin (QE) or epigallocatechin gallate (EGCG) for 5 hours followed by methotrexate. Cytotoxicity was measured using the MTT assay or resazurin fluorescence assay. ROS was determined using the 2’, 7’-dichlorofluorescein diacetate assay. Intracellular GSH was measured using the monochlorobimane assay. Results: Methotrexate was cytotoxic to MDA-MB-231 cells with IC50 of 35±4 µM. The IC50 value was 68±9.4 µM with QE and 83±16 µM for EGCG. The pre-treatment with QE and EGCG lowered the IC50 for methotrexate by 28% (P =0.009) and 16% (P=0.2027). Intracellular ROS concentrations increased after treatment with methotrexate, QE or EGCG singly and ROS decreased with combination treatment compared with the response for methotrexate only. There were no significant changes in intracellular GSH. Conclusion: Pretreatment with tea polyphenols partially sensitized breast cancer cells towards methotrexate and decreases intracellular ROS. More research is needed to optimize the sensitizing effect of tea phenols on the breast cancer cell response to methotrexate.  

Breast cancer methotrexate quercetin epigallocatechin gallate oxidative stress anticancer effect

References (14)

  1. 1 Rapid colorimetric assay for cell growth and survival [DOI]
  2. 2 Multitargeted cancer prevention by quercetin [DOI]
  3. 3 Quercetin-induced apoptosis acts through mitochondrial- and caspase-3-dependent pathways in human breast cancer MDA-MB-231 cells [DOI]
  4. 4 Green tea polyphenol epigallocatechin-3-gallate (EGCG) as adjuvant in cancer therapy [DOI]
  5. 5 Advances in individual prediction of methotrexate toxicity: a review [DOI]
  6. 6 Cancer Biology and Hormesis: Human Tumor Cell Lines Commonly Display Hormetic (Biphasic) Dose Responses [DOI]
  7. 7 Research Strategies in the Study of the Pro-Oxidant Nature of Polyphenol Nutraceuticals [DOI]
  8. 8 Methylation-dependent Silencing of the Reduced Folate Carrier Gene in Inherently Methotrexate-resistant Human Breast Cancer Cells [DOI]
  9. 9 Chickpea (Cicer arietinum) and Other Plant-Derived Protease Inhibitor Concentrates Inhibit Breast and Prostate Cancer Cell Proliferation In Vitro [DOI]
  10. 10 Intervention of α-lipoic acid ameliorates methotrexate-induced oxidative stress and genotoxicity: A study in rat intestine [DOI]
  11. 11 Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats [DOI]
  12. 12 Augmented sensitivity to methotrexate by curcumin induced overexpression of folate receptor in KG-1 cells [DOI]
  13. 13 Development of methotrexate proline prodrug to overcome resistance by MDA-MB-231 cells [DOI]
  14. 14 In vitro mechanism of action for the cytotoxicity elicited by the combination of epigallocatechin gallate and raloxifene in MDA-MB-231 cells [DOI]

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