Pyrophen isolated from the endophytic fungus aspergillus fumigatus strain karsv04 synergizes the effect of doxorubicin in killing mcf7 but not t47d cells

Abstract

Objectives: Pyrophen, an amino acid-pyrone derivative isolated from Aspergillus fumigatus strain KARSV04 has been reported to have an anticancer effect on T47D cells by inhibiting the growth of cells and modulating the cell cycle in the S phase. In the present study, the effect of pyrophen in doxorubicin (Dox) chemotherapy in an in vitro model of breast cancers was studied. Materials and Methods: The cytotoxicity of pyrophen and Dox separately and in combination were evaluated in T47D and MCF-7 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Modulation of cell cycle distribution and apoptosis was examined by flow cytometry. Results: Our findings showed that pyrophen did not significantly potentiate Dox-induced cytotoxicity in T47D cells. Adding Dox-treated T47D cells with pyrophen at a concentration of 9.20 µg/mL induced a slight increase in the S-phase cell population. This compound induced cytotoxicity of MCF-7 cells with IC50 of 70.57 µg/mL. Co-treatment of pyrophen and Dox in MCF-7 cells increased cytotoxicity relative to Dox alone, which was suggested in part to be due to modulation of the cell cycle in the G2/M phase and apoptosis. Conclusion: The data suggest different mechanisms of regulation in promoting cell death by two different cell lines in response to administration of pyrophen.