Repository of Research and Investigative Information

Repository of Research and Investigative Information

Hormozgan University of Medical Sciences

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

(2018) Acriflavine enhances the antitumor activity of the chemotherapeutic drug 5‑fluorouracil in colorectal cancer cells. Oncology Letters.

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Abstract

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 (IC30) of ACF and various concentrations of 5-FU, or pretreated with the IC30 of ACF and various concentrations of 5-FU. To assess the mechanism of action of ACF, cells were treated with IC30 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. © 2018, Spandidos Publications. All rights reserved.

Item Type: Article
Additional Information: cited By 0
Keywords: acriflavine; DNA topoisomerase (ATP hydrolysing); fluorouracil; hypoxia inducible factor 1alpha; irinotecan; messenger RNA; protein p53, antineoplastic activity; Article; cancer chemotherapy; cell viability; colorectal cancer; colorectal cancer cell line; controlled study; cytotoxicity; drug sensitivity; gene mutation; human; human cell; IC50; MTT assay; overall survival; protein expression; real time polymerase chain reaction; reverse transcription polymerase chain reaction; RNA extraction
Subjects: QU Biochemistry. Cell Biology and Genetics > QU 300-560 Cell Biology and Genetics
QY Clinical Laboratory Pathology > QY 400-490 Hematologic Tests. Blood Chemical Analysis
QZ Pathology > QZ 200-380 Neoplasms
Divisions: Education Vice-Chancellor Department > Faculty of Medicine > Department of Basic Science > Department of Physiology Medical
Research Vice-Chancellor Department > Student Research Committee
Research Vice-Chancellor Department > Molecular Medicine Research Center
Depositing User: مهندس هدی فهیم پور
URI: http://eprints.hums.ac.ir/id/eprint/5658

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