Dietary polyphenols influence antimetabolite agents: methotrexate, 6-mercaptopurine and 5-fluorouracil in leukemia cell lines

MAHBUB, Amani, LE MAITRE, Christine, HAYWOOD-SMALL, Sarah, CROSS, Neil and JORDAN-MAHY, Nikki (2017). Dietary polyphenols influence antimetabolite agents: methotrexate, 6-mercaptopurine and 5-fluorouracil in leukemia cell lines. Oncotarget, 8 (37).

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Abstract

Polyphenols have been previously shown to sensitize leukemia cell lines to topoisomerase inhibitors. Here, we assess the effects of five polyphenols when used alone and in combination with antimetabolites: methotrexate, 6-mercaptopurine and 5-fluorouracil; in lymphoid and myeloid leukemia cells lines, and non-tumor control cells. The effects of combined treatments were investigated on ATP and glutathione levels, cell-cycle progression, DNA damage and apoptosis. Polyphenols antagonized methotrexate and 6-mercaptopurine induced cell-cycle arrest and apoptosis in most leukemia cell lines. This was associated with reduced DNA damage and increased glutathione levels, greater than that seen following individual treatments alone. In contrast, 5-fluorouracil when combined with quercetin, apigenin and rhein caused synergistic decrease in ATP levels, induction of cell-cycle arrest and apoptosis in some leukemia cell lines. However, antagonistic effects were observed when 5-fluorouracil was combined with rhein and cis-stilbene in myeloid cell lines. The effects were dependant on polyphenol type and chemotherapy agent investigated, and cell type treated. Interestingly treatment of non-tumor control cells with polyphenols protected cells from antimetabolite treatments. This suggests that polyphenols modulate the action of antimetabolite agents; more importantly they antagonized methotrexate and 6-mercaptopurine actions, thus suggesting the requirement of polyphenol-exclusion during their use.

Item Type: Article
Uncontrolled Keywords: Leukaemia, polyphenols methotrexate, 6-metcaptopurine, 5-fluorouracil
Research Institute, Centre or Group: Biomolecular Sciences Research Centre
Departments: Health and Well-being > Bioscience
Identification Number: 10.18632/oncotarget.20501
Depositing User: Nikki Jordan-Mahy
Date Deposited: 13 Sep 2017 10:48
Last Modified: 13 Sep 2017 10:55
URI: http://shura.shu.ac.uk/id/eprint/16707

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