Higginsianins A and B, two fungal diterpenoid α-pyrones with cytotoxic activity against human cancer cells
| Autor: | Felicia Sangermano, Viola Calabrò, Antonio Evidente, Alessio Cimmino, Marco Masi, Maria Vivo, Peravali Ravindra, Alessandra Pollice |
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| Přispěvatelé: | Sangermano, Felicia, Masi, Marco, Vivo, Maria, Ravindra, Peravali, Cimmino, Alessio, Pollice, Alessandra, Evidente, Antonio, Calabrò, Viola |
| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
Cell death Higginsianins 0301 basic medicine Cancer cells Cell Survival Cell Antineoplastic Agents Cancer cell Toxicology Cell Line Cell cycle arrest HeLa 03 medical and health sciences 0302 clinical medicine medicine Humans Cytotoxic T cell Anticancer metabolites Colletotrichum higginsianum DNA Damage Diterpenes biology Cell growth Chemistry General Medicine Cell cycle biology.organism_classification Molecular biology HaCaT 030104 developmental biology medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis Anticancer metabolite |
| Zdroj: | Toxicology in Vitro. 61:104614 |
| ISSN: | 0887-2333 |
| DOI: | 10.1016/j.tiv.2019.104614 |
| Popis: | Two new diterpenoid α-pyrones, named higginsianins A and B, were isolated from the mycelium of the microbial fungus Colletotrichum higginsianum grown in liquid culture. In previous studies, we have shown that both compounds reduce viability of different types of cancer cells in culture. Here, we extend our previous observations and explore, at a deeper level, the cellular effects of higginsianins treatment. Higginisianins A and B reduce viability of A431, HeLa and H1299 cancer cells. Both compounds increase the level of the cell cycle inhibitor p21WAF and reduce the rate of cell proliferation. Cell cycle analyses reveal that higginsianins arrest cancer cells in S-phase. Furthermore, cells incubated with higginsianins reveal discrete γ-H2AX positive nuclear foci indicating the occurrence of DNA lesions. At longer incubation times, higginsianins induce massive cell detachment and non-apoptotic cell death. Human primary keratinocytes and spontaneously immortalized Hacat cells, a preneoplastic cell line model, are less sensitive to higginsianins effects. These findings suggest that higginsianins exhibit considerable cytotoxicity against a wide spectrum of malignant cells and may be considered as promising anticancer agents. |
| Databáze: | OpenAIRE |
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