Astuti Puji, Januarti Ika Buana, Kiromah Naelaz Zukhruf Wakhidatul, Fitri Hidayah Anisa, Wahyono Wahyono, Wahyuono Subagus
Universitas Gadjah Mada Faculty of Pharmacy, Department of Pharmaceutical Biology, Yogyakarta, Indonesia.
Sultan Agung Islamic University Faculty of Medicine, Pharmacy College, Semarang, Indonesia.
Turk J Pharm Sci. 2020 Jun;17(3):280-284. doi: 10.4274/tjps.galenos.2019.30633. Epub 2020 Jun 22.
Pyrophen, an amino acid-pyrone derivative isolated from 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 model of breast cancers was studied.
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.
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 IC 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.
The data suggest different mechanisms of regulation in promoting cell death by two different cell lines in response to administration of pyrophen.
据报道，从菌株KARSV04中分离出的氨基酸吡喃酮衍生物Pyrophen通过抑制细胞生长和调节S期细胞周期，对T47D细胞具有抗癌作用。在本研究中，研究了Pyrophen在乳腺癌模型中对阿霉素（Dox）化疗的影响。
采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法，分别评估Pyrophen和Dox单独及联合使用对T47D和MCF-7细胞的细胞毒性。通过流式细胞术检测细胞周期分布和凋亡的调节情况。
我们的研究结果表明，Pyrophen在T47D细胞中并未显著增强Dox诱导的细胞毒性。向经Dox处理的T47D细胞中添加浓度为9.20μg/mL的Pyrophen，可使S期细胞群体略有增加。该化合物对MCF-7细胞具有细胞毒性，IC50为70.57μg/mL。在MCF-7细胞中，Pyrophen与Dox联合处理相对于单独使用Dox增加了细胞毒性，这部分归因于对G2/M期细胞周期的调节和凋亡。
数据表明，两种不同细胞系对Pyrophen给药的反应中，促进细胞死亡的调节机制不同。
