Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5-fluorouracil in colorectal cancer cells.

Oncol Lett 2018 Jun 25;15(6):10084-10090. Epub 2018 Apr 25.

Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas 7919915519, Iran.

5-Fluorouracil (5-FU)-based chemotherapy improves the overall survival rates of patients with colorectal cancer (CRC). However, only a small proportion of patients respond to 5-FU when used as a single agent. The aim of the present study was to investigate whether the anticancer property of 5-FU is potentiated by combination treatment with acriflavine (ACF) in CRC cells. Additionally, the potential underlying molecular mechanisms of the cytotoxic effect of ACF were determined. The cytotoxic effects of ACF, 5-FU and irinotecan on different CRC cell lines with different p53 status were investigated using an MTT assay. SW480 cells that express a mutated form of p53 and two other CRC cell lines were used, HCT116 and LS174T, with wild-type p53. To determine the effect of ACF on the sensitivity of cells to 5-FU, cells were co-treated with the 30% maximal inhibitory concentration (IC) of ACF and various concentrations of 5-FU, or pretreated with the IC of ACF and various concentrations of 5-FU. To assess the mechanism of action of ACF, cells were treated with IC values of the compound and then the reverse transcription-quantitative polymerase chain reaction was used to evaluate mRNA levels of hypoxia-inducible factor-1α (HIF-1α) and topoisomerase 2. Results indicate that pretreatment with ACF markedly sensitized CRC cells to the cytotoxic effects of 5-FU, whereas simultaneous treatment with ACF and 5-FU were not able to alter the resistance of CRC cells to 5-FU. In comparison with irinotecan, ACF was a more potent agent for enhancing the antitumor activity of 5-FU. ACF did not alter the mRNA levels of either HIF-1α or topoisomerase 2. The results of the present study reveal for the first time that pretreatment of CRC cells with ACF markedly increases the cytotoxic effects of 5-FU, regardless of the p53 status of cells.

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Source
http://dx.doi.org/10.3892/ol.2018.8569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6004650PMC
June 2018

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