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

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• Polyphenols are known to sensitize leukemia cells to certain chemotherapy drugs.
• Antimetabolites like methotrexate, 6-mercaptopurine, and 5-fluorouracil are common leukemia treatments.

Purpose of the Study:

• To investigate the combined effects of five polyphenols with three antimetabolites on leukemia and control cells.
• To determine how these combinations affect cellular processes including ATP levels, glutathione, cell-cycle, DNA damage, and apoptosis.

Main Methods:

• Exposure of lymphoid and myeloid leukemia cell lines, and non-tumor control cells to individual polyphenols and antimetabolites, as well as their combinations.
• Assessment of ATP and glutathione levels, cell-cycle progression, DNA damage, and apoptosis following treatments.

Main Results:

• Polyphenols antagonized methotrexate and 6-mercaptopurine in most leukemia cell lines, reducing DNA damage and increasing glutathione.
• Combinations of 5-fluorouracil with quercetin, apigenin, and rhein showed synergistic effects in some leukemia cells, decreasing ATP and inducing apoptosis.
• Antagonistic effects were noted for 5-fluorouracil with rhein and cis-stilbene in myeloid cells; polyphenols also protected non-tumor cells.

Conclusions:

• Polyphenols modulate antimetabolite efficacy, with effects varying by polyphenol, antimetabolite, and cell type.
• Polyphenols antagonize methotrexate and 6-mercaptopurine, indicating a need to exclude them during treatment with these drugs.
• The protective effect on non-tumor cells suggests differential impacts on cancer versus healthy cells.