Chromomycin A2 Induces Autophagy in Melanoma Cells
The present study highlights the biological effects of chromomycin A2 toward metastatic melanoma cells in culture. Besides chromomycin A2, chromomycin A3 and demethylchromomycin A2 were also identified from the extract derived from Streptomyces sp., recovered from Paracuru Beach, located in the nort...
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| Format: | Article |
| Language: | English |
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MDPI AG
2014-12-01
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| Series: | Marine Drugs |
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| Online Access: | http://www.mdpi.com/1660-3397/12/12/5839 |
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| author | Larissa Alves Guimarães Paula Christine Jimenez Thiciana da Silva Sousa Hozana Patrícia S. Freitas Danilo Damasceno Rocha Diego Veras Wilke Jesús Martín Fernando Reyes Otília Deusdênia Loiola Pessoa Letícia Veras Costa-Lotufo |
| author_facet | Larissa Alves Guimarães Paula Christine Jimenez Thiciana da Silva Sousa Hozana Patrícia S. Freitas Danilo Damasceno Rocha Diego Veras Wilke Jesús Martín Fernando Reyes Otília Deusdênia Loiola Pessoa Letícia Veras Costa-Lotufo |
| author_sort | Larissa Alves Guimarães |
| collection | DOAJ |
| description | The present study highlights the biological effects of chromomycin A2 toward metastatic melanoma cells in culture. Besides chromomycin A2, chromomycin A3 and demethylchromomycin A2 were also identified from the extract derived from Streptomyces sp., recovered from Paracuru Beach, located in the northeast region of Brazil. The cytotoxic activity of chromomycin A2 was evaluated across a panel of human tumor cell lines, which found IC50 values in the nM-range for exposures of 48 and 72 h. MALME-3M, a metastatic melanoma cell line, showed the highest sensitivity to chromomycin A2 after 48h incubation, and was chosen as a model to investigate this potent cytotoxic effect. Treatment with chromomycin A2 at 30 nM reduced cell proliferation, but had no significant effect upon cell viability. Additionally, chromomycin A2 induced accumulation of cells in G0/G1 phase of the cell cycle, with consequent reduction of S and G2/M and unbalanced expression of cyclins. Chromomycin A2 treated cells depicted several cellular fragments resembling autophagosomes and increased expression of proteins LC3-A and LC3-B. Moreover, exposure to chromomycin A2 also induced the appearance of acidic vacuolar organelles in treated cells. These features combined are suggestive of the induction of autophagy promoted by chromomycin A2, a feature not previously described for chromomycins. |
| first_indexed | 2024-04-13T06:57:01Z |
| format | Article |
| id | doaj.art-7ab0f89a12b04b10a7d9799b71f368fb |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T06:57:01Z |
| publishDate | 2014-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-7ab0f89a12b04b10a7d9799b71f368fb2022-12-22T02:57:13ZengMDPI AGMarine Drugs1660-33972014-12-0112125839585510.3390/md12125839md12125839Chromomycin A2 Induces Autophagy in Melanoma CellsLarissa Alves Guimarães0Paula Christine Jimenez1Thiciana da Silva Sousa2Hozana Patrícia S. Freitas3Danilo Damasceno Rocha4Diego Veras Wilke5Jesús Martín6Fernando Reyes7Otília Deusdênia Loiola Pessoa8Letícia Veras Costa-Lotufo9Marine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, BrazilMarine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, BrazilDepartment of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, BrazilDepartment of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, BrazilDepartment of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Ceará 60430-270, BrazilMarine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, BrazilFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada 18016, SpainFundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada 18016, SpainDepartment of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, BrazilMarine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, BrazilThe present study highlights the biological effects of chromomycin A2 toward metastatic melanoma cells in culture. Besides chromomycin A2, chromomycin A3 and demethylchromomycin A2 were also identified from the extract derived from Streptomyces sp., recovered from Paracuru Beach, located in the northeast region of Brazil. The cytotoxic activity of chromomycin A2 was evaluated across a panel of human tumor cell lines, which found IC50 values in the nM-range for exposures of 48 and 72 h. MALME-3M, a metastatic melanoma cell line, showed the highest sensitivity to chromomycin A2 after 48h incubation, and was chosen as a model to investigate this potent cytotoxic effect. Treatment with chromomycin A2 at 30 nM reduced cell proliferation, but had no significant effect upon cell viability. Additionally, chromomycin A2 induced accumulation of cells in G0/G1 phase of the cell cycle, with consequent reduction of S and G2/M and unbalanced expression of cyclins. Chromomycin A2 treated cells depicted several cellular fragments resembling autophagosomes and increased expression of proteins LC3-A and LC3-B. Moreover, exposure to chromomycin A2 also induced the appearance of acidic vacuolar organelles in treated cells. These features combined are suggestive of the induction of autophagy promoted by chromomycin A2, a feature not previously described for chromomycins.http://www.mdpi.com/1660-3397/12/12/5839Streptomycesautophagycytotoxicitychromomycinmarine microorganismsBrazil |
| spellingShingle | Larissa Alves Guimarães Paula Christine Jimenez Thiciana da Silva Sousa Hozana Patrícia S. Freitas Danilo Damasceno Rocha Diego Veras Wilke Jesús Martín Fernando Reyes Otília Deusdênia Loiola Pessoa Letícia Veras Costa-Lotufo Chromomycin A2 Induces Autophagy in Melanoma Cells Marine Drugs Streptomyces autophagy cytotoxicity chromomycin marine microorganisms Brazil |
| title | Chromomycin A2 Induces Autophagy in Melanoma Cells |
| title_full | Chromomycin A2 Induces Autophagy in Melanoma Cells |
| title_fullStr | Chromomycin A2 Induces Autophagy in Melanoma Cells |
| title_full_unstemmed | Chromomycin A2 Induces Autophagy in Melanoma Cells |
| title_short | Chromomycin A2 Induces Autophagy in Melanoma Cells |
| title_sort | chromomycin a2 induces autophagy in melanoma cells |
| topic | Streptomyces autophagy cytotoxicity chromomycin marine microorganisms Brazil |
| url | http://www.mdpi.com/1660-3397/12/12/5839 |
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