Chromomycin A2 Induces Autophagy in Melanoma Cells

Chromomycin A2 Induces Autophagy in Melanoma Cells

Author Guimaraes, Larissa Alves Google Scholar
Jimenez, Paula Christine Autor UNIFESP Google Scholar
Silva Sousa, Thiciana da Google Scholar
Freitas, Hozana Patricia S. Google Scholar
Rocha, Danilo Damasceno Google Scholar
Wilke, Diego Veras Google Scholar
Martin, Jesus Google Scholar
Reyes, Fernando Google Scholar
Loiola Pessoa, Otilia Deusdenia Google Scholar
Costa-Lotufo, Leticia Veras Google Scholar
Institution Univ Fed Ceara
Universidade Federal de São Paulo (UNIFESP)
Fdn MEDINA
Abstract 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 G(0)/G(1) phase of the cell cycle, with consequent reduction of S and G(2)/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.
Keywords Streptomyces
autophagy
cytotoxicity
chromomycin
marine microorganisms
Brazil
Language English
Sponsor Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundacao Cearense de Apoio ao Desenvolvimento Cientifico e Tecnologico (FUNCAP-Programa Areas Estrategicas)
Date 2014-12-01
Published in Marine Drugs. Basel: Mdpi Ag, v. 12, n. 12, p. 5839-5855, 2014.
ISSN 1660-3397 (Sherpa/Romeo, impact factor)
Publisher Mdpi Ag
Extent 5839-5855
Origin http://dx.doi.org/10.3390/md12125839
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000346796500006
URI http://repositorio.unifesp.br/handle/11600/38488

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