Methotrexate combination effects with genistein and daidzein on MDA-MB-231 breast cancer cell viability

Ashleigh Maginnes, Richard K. Owusu-Apenten

Research output: Contribution to journalArticle

Abstract

Aims: To investigate the effect of methotrexate and soy isoflavones genistein and daidzein on MDA-MB-231 breast cancer cell viability. Study Design: In-vitro study using cultured cellsPlace and Duration of Study: Nutrition Innovations Centre for Food & Health (NICHE), School of Biomedical Sciences, Ulster University, data collected September 2014-2015.Methods: Human breast cancer MDA-MB-231 cells were cultured in DMEM (with 10% FBS, 1% Pen strep) and treated with methotrexate, genistein or daidzein for 72 hrs. Combinations treatments used non-fixed ratios of methotrexate (0-100 μM) and genistein or daidzein (30 μM) with cell viability monitored using the MTT assay. Results: The 50% effect dose (EC50) was 44.7±6.4 μM for methotrexate, 55.8±3.9 μM for genistein or 67.4±12.2 μM for daidzein. Combination treatments with genistein or daidzein produced EC50 of 57.6±2.0 or 29.7±2.4 μM for methotrexate, respectively. The combination index (CI) was 1.9 for methotrexate-genistein whilst CI was 1.1 for methotrexate-daidzein near the median dose. Values for CI decreased from 5.0 towards 1.0 as the ratio of methotrexate: isoflavone increased. The results are discussed in terms of prevailing ideas concerning how phytochemicals affects drug adsorption, distribution, metabolism and excretion (ADME) and the expected consequences for cytotoxicity.Conclusions: Treatment of MDA-MB-231 breast cancer cells with methotrexate and genistein or daidzein produces interactions consistent with antagonism (CI =1.1-5.0) but the effects are predicted to diminish with rising methotrexate to isoflavone ratio.
LanguageEnglish
Pages1-9
JournalJournal of Applied Life Sciences International
Volume13
Issue number1
Publication statusPublished - 25 Jul 2017

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Genistein
Methotrexate
Cell Survival
Breast Neoplasms
Isoflavones
daidzein
School Health Services
Phytochemicals
Adsorption
Cultured Cells
Food

Keywords

  • Methotrexate
  • breast cancer
  • isoflavones
  • genistein
  • daidzein
  • interactions.

Cite this

@article{c31c93fdb25f4ce09949a1fd918e7e07,
title = "Methotrexate combination effects with genistein and daidzein on MDA-MB-231 breast cancer cell viability",
abstract = "Aims: To investigate the effect of methotrexate and soy isoflavones genistein and daidzein on MDA-MB-231 breast cancer cell viability. Study Design: In-vitro study using cultured cellsPlace and Duration of Study: Nutrition Innovations Centre for Food & Health (NICHE), School of Biomedical Sciences, Ulster University, data collected September 2014-2015.Methods: Human breast cancer MDA-MB-231 cells were cultured in DMEM (with 10{\%} FBS, 1{\%} Pen strep) and treated with methotrexate, genistein or daidzein for 72 hrs. Combinations treatments used non-fixed ratios of methotrexate (0-100 μM) and genistein or daidzein (30 μM) with cell viability monitored using the MTT assay. Results: The 50{\%} effect dose (EC50) was 44.7±6.4 μM for methotrexate, 55.8±3.9 μM for genistein or 67.4±12.2 μM for daidzein. Combination treatments with genistein or daidzein produced EC50 of 57.6±2.0 or 29.7±2.4 μM for methotrexate, respectively. The combination index (CI) was 1.9 for methotrexate-genistein whilst CI was 1.1 for methotrexate-daidzein near the median dose. Values for CI decreased from 5.0 towards 1.0 as the ratio of methotrexate: isoflavone increased. The results are discussed in terms of prevailing ideas concerning how phytochemicals affects drug adsorption, distribution, metabolism and excretion (ADME) and the expected consequences for cytotoxicity.Conclusions: Treatment of MDA-MB-231 breast cancer cells with methotrexate and genistein or daidzein produces interactions consistent with antagonism (CI =1.1-5.0) but the effects are predicted to diminish with rising methotrexate to isoflavone ratio.",
keywords = "Methotrexate, breast cancer, isoflavones, genistein, daidzein, interactions.",
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Methotrexate combination effects with genistein and daidzein on MDA-MB-231 breast cancer cell viability. / Maginnes, Ashleigh; Owusu-Apenten, Richard K.

In: Journal of Applied Life Sciences International, Vol. 13, No. 1, 25.07.2017, p. 1-9.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methotrexate combination effects with genistein and daidzein on MDA-MB-231 breast cancer cell viability

AU - Maginnes, Ashleigh

AU - Owusu-Apenten, Richard K.

PY - 2017/7/25

Y1 - 2017/7/25

N2 - Aims: To investigate the effect of methotrexate and soy isoflavones genistein and daidzein on MDA-MB-231 breast cancer cell viability. Study Design: In-vitro study using cultured cellsPlace and Duration of Study: Nutrition Innovations Centre for Food & Health (NICHE), School of Biomedical Sciences, Ulster University, data collected September 2014-2015.Methods: Human breast cancer MDA-MB-231 cells were cultured in DMEM (with 10% FBS, 1% Pen strep) and treated with methotrexate, genistein or daidzein for 72 hrs. Combinations treatments used non-fixed ratios of methotrexate (0-100 μM) and genistein or daidzein (30 μM) with cell viability monitored using the MTT assay. Results: The 50% effect dose (EC50) was 44.7±6.4 μM for methotrexate, 55.8±3.9 μM for genistein or 67.4±12.2 μM for daidzein. Combination treatments with genistein or daidzein produced EC50 of 57.6±2.0 or 29.7±2.4 μM for methotrexate, respectively. The combination index (CI) was 1.9 for methotrexate-genistein whilst CI was 1.1 for methotrexate-daidzein near the median dose. Values for CI decreased from 5.0 towards 1.0 as the ratio of methotrexate: isoflavone increased. The results are discussed in terms of prevailing ideas concerning how phytochemicals affects drug adsorption, distribution, metabolism and excretion (ADME) and the expected consequences for cytotoxicity.Conclusions: Treatment of MDA-MB-231 breast cancer cells with methotrexate and genistein or daidzein produces interactions consistent with antagonism (CI =1.1-5.0) but the effects are predicted to diminish with rising methotrexate to isoflavone ratio.

AB - Aims: To investigate the effect of methotrexate and soy isoflavones genistein and daidzein on MDA-MB-231 breast cancer cell viability. Study Design: In-vitro study using cultured cellsPlace and Duration of Study: Nutrition Innovations Centre for Food & Health (NICHE), School of Biomedical Sciences, Ulster University, data collected September 2014-2015.Methods: Human breast cancer MDA-MB-231 cells were cultured in DMEM (with 10% FBS, 1% Pen strep) and treated with methotrexate, genistein or daidzein for 72 hrs. Combinations treatments used non-fixed ratios of methotrexate (0-100 μM) and genistein or daidzein (30 μM) with cell viability monitored using the MTT assay. Results: The 50% effect dose (EC50) was 44.7±6.4 μM for methotrexate, 55.8±3.9 μM for genistein or 67.4±12.2 μM for daidzein. Combination treatments with genistein or daidzein produced EC50 of 57.6±2.0 or 29.7±2.4 μM for methotrexate, respectively. The combination index (CI) was 1.9 for methotrexate-genistein whilst CI was 1.1 for methotrexate-daidzein near the median dose. Values for CI decreased from 5.0 towards 1.0 as the ratio of methotrexate: isoflavone increased. The results are discussed in terms of prevailing ideas concerning how phytochemicals affects drug adsorption, distribution, metabolism and excretion (ADME) and the expected consequences for cytotoxicity.Conclusions: Treatment of MDA-MB-231 breast cancer cells with methotrexate and genistein or daidzein produces interactions consistent with antagonism (CI =1.1-5.0) but the effects are predicted to diminish with rising methotrexate to isoflavone ratio.

KW - Methotrexate

KW - breast cancer

KW - isoflavones

KW - genistein

KW - daidzein

KW - interactions.

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