Pyrophen isolated from endophytic fungi Aspergillus fumigatus strain KARSV04 synergizes the effect of doxorubicin in killing MCF7 but not T47D cells

Abstract

Introduction: Pyrophen, an amino acid-pyrone derivative isolated from Aspergillus fumigatus strain KARSV04 has been reported to exhibit anticancer effect on T47D cells by inhibiting the growth of the cells and modulate the cell cycle on S phase. Present study, effect of pyrophen in the doxorubicin (Dox) chemotherapy on an in vitro model of breast cancers was studied. Methods: The cytotoxicity of pyrophen, doxorubicin and in combination were evaluated in T47D and MCF-7 cells using MTT assay. Modulation on 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 concentration of 9.20 µg/mL induced slight increase of 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 due to modulation of cell cycle at 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.u n c o r r e c t e d p r o o f u n c o r r e c t e d p r o o f 2 ÖZAmaç: Aspergillus fumigatus KARSV04'ten izole edilen amino asit-piron türevi olan pirofen, hücrelerin büyümesini engeller ve S fazındaki hücre döngüsünü modüle ederek T47D hücreleri üzerinde antikanser etkisi gösterdiği rapor edilmiştir. Bu çalışmada, doksorubisin (Dox) kemoterapisindeki pirofen meme kanseri modelinde "in vitro" modeli üzerindeki etkisi incelenmiştir. Metotlar: Pirofen, doksorubisin ve kombinasyon halindeki sitotoksisite, MTT tahlili kullanılarak T47D ve MCF-7 hücrelerinde değerlendirildi. Hücre döngüsü dağılımı ve apoptozis modülasyonu akış sitometrisi ile incelendi. Bulgular: Bulgularımız, pirofen, T47D hücrelerinde Dox kaynaklı sitotoksisiteyi önemli ölçüde artırmadığını gösterdi. Pirofen eklenmesi, 9.20 µg/mL konsantrasyonunda Dox ile muamele edilmiş T47D hücrelerine S-faz hücre popülasyonunda hafif bir artışa neden oldu. Bu bileşik, IC50 70.57 µg/mL olan MCF-7 hücrelerinin sitotoksisitesini tesir etmistir. MCF-7 hücrelerinde pirofen ve Dox'un birlikte işlenmesi, sadece Dox ile karşılaştırıldığında sitotoksisiteyi arttırmıştır; bu, kısmen G2/M fazındaki hücre döngüsünün modülasyonu ve apoptoz nedeniyle önerilmiştir. Sonuç: Veriler, pirofen uygulamasına cevap olarak iki farklı hücre çizgisi tarafından hücre ölümünü teşvik etmede farklı düzenleme mekanizmaları olduğunu göstermektedir.

Cytotoxicity of Combination Doxorubicin and <i>Garcinia picrorrhiza</i> Fruit Extract on Fibroblast Cell

“…9 Combination of pyrophen fraction of endophyte fungus-doxorubicin showed a synergistic effect in antiproliferative, cell cycle, and apoptotic induction properties MCF-7. 10 However, it remains unclear the effect of Garcinia picrorrhiza fruit ethanolic extract (GpKar) on normal cells except on Vero cells. The combination of doxorubicin and GpKar is expected to be toxic to cancer cells.…”

Study of the culture medium variation in the production of secondary metabolite pyrophen by endophytic fungus Aspergillus niger from Harconia speciosa

“…Therefore, the natural product pyrophen (1), a pyrone derivative from Lphenylalanine, was first isolated from Aspergillus niger (Barnes et al, 2003). Pyrophen (1) has been isolated from other Aspergillus species, such as Alternaria alternata (Astuti et al, 2016;Astuti et al, 2020;Hai et al, 2020). This compound has shown anticancer activity, and various studies on its synthesis and biological activity have been previously reported (Reber et al, 2018;Quang et al, 2022).…”