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Mar. Drugs 2014, 12(12), 5839-5855;

Chromomycin A2 Induces Autophagy in Melanoma Cells

Marine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, Brazil
Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Ceará 60430-270, Brazil
Marine Sciences Department, Federal University of São Paulo, Santos, São Paulo 11030-400, Brazil
Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, Brazil
Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada 18016, Spain
Author to whom correspondence should be addressed.
Received: 22 August 2014 / Revised: 17 November 2014 / Accepted: 20 November 2014 / Published: 4 December 2014
(This article belongs to the Special Issue Bioactive Compounds from Marine Microbes)
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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. View Full-Text
Keywords: Streptomyces; autophagy; cytotoxicity; chromomycin; marine microorganisms; Brazil Streptomyces; autophagy; cytotoxicity; chromomycin; marine microorganisms; Brazil

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Guimarães, L.A.; Jimenez, P.C.; Sousa, T.S.; Freitas, H.P.S.; Rocha, D.D.; Wilke, D.V.; Martín, J.; Reyes, F.; Deusdênia Loiola Pessoa, O.; Costa-Lotufo, L.V. Chromomycin A2 Induces Autophagy in Melanoma Cells. Mar. Drugs 2014, 12, 5839-5855.

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