Polyethers isolated from the marine actinobacterium Streptomyces cacaoi inhibit autophagy and induce apoptosis in cancer cells
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Tarih
2019
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Ireland Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Polyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1–3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies. As several polyether compounds with structural similarity such as monensin have been linked with autophagy and cell death, we first assessed the cytotoxicity of these three compounds. Compounds 2 and 3, but not 1, were found to be cytotoxic in several cell lines with a higher potency towards cancer cells. Furthermore, 2 and 3 caused accumulation of both autophagy flux markers LC3-II and p62 along with cleavage of caspase-3, caspase-9 and poly (ADP-ribose)polymerase 1 (PARP-1). Interestingly, prolonged treatment of the compounds caused a dramatic downregulation of the proteins related to autophagasome formation in a dose dependent manner. Our findings provide insights on the molecular mechanisms of the polyether-type polyketides, and signify their potency as chemotherapeutic agents through inhibiting autophagy and inducing apoptosis. © 2019 Elsevier B.V.
Açıklama
Anahtar Kelimeler
Apoptosis, Autophagy, Marine actinobacterium polyether antibiotic
Kaynak
Chemico-Biological Interactions
WoS Q Değeri
Scopus Q Değeri
Q1
Cilt
307
