title: Chromomycin A2 induces autophagy in melanoma cells.
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 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.
authors.affiliation: Marine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, Brazil. larissaalvesgui@gmail.com.
authors.forename: Larissa Alves
authors.initials: LA
authors.lastname: Guimarães
authors.affiliation: Marine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, Brazil. paulacjimenez@gmail.com.
authors.forename: Paula Christine
authors.initials: PC
authors.lastname: Jimenez
authors.affiliation: Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, Brazil. thicy85@yahoo.com.br.
authors.forename: Thiciana da Silva
authors.initials: Tda S
authors.lastname: Sousa
authors.affiliation: Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, Brazil. hpatriciasf@yahoo.com.br.
authors.forename: Hozana Patrícia S
authors.initials: HP
authors.lastname: Freitas
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceara, Fortaleza, Ceará 60430-270, Brazil. danilodrocha@yahoo.com.br.
authors.forename: Danilo Damasceno
authors.initials: DD
authors.lastname: Rocha
authors.affiliation: Marine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, Brazil. diegowilke@gmail.com.
authors.forename: Diego Veras
authors.initials: DV
authors.lastname: Wilke
authors.affiliation: Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada 18016, Spain. jesus.martin@medinaandalucia.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Martín
authors.affiliation: Fundación MEDINA, Centro de Excelencia en Investigación de Medicamentos Innovadores en Andalucía, Granada 18016, Spain. fernando.reyes@medinaandalucia.es.
authors.forename: Fernando
authors.initials: F
authors.lastname: Reyes
authors.affiliation: Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza, CE 60021-970, Brazil. opessoa@ufc.br.
authors.forename: Otília
authors.initials: O
authors.lastname: Deusdênia Loiola Pessoa
authors.affiliation: Marine Sciences Institute, Federal University of Ceara, Fortaleza, Ceara 60165-081, Brazil. costalotufo@gmail.com.
authors.forename: Letícia Veras
authors.initials: LV
authors.lastname: Costa-Lotufo
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D001938:Brazil; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D014128:Chromomycin A3 / Q000378:metabolism; D002865:Chromomycins / Q000494:pharmacology; D045325:HCT116 Cells; D018922:HL-60 Cells; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008926:Plicamycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013302:Streptomyces / Q000737:chemistry
chemical_list: D002865:Chromomycins; C477012:MAP1LC3A protein, human; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; C000594480:chromomycin A2; C055114:demethylchromomycin A2; D014128:Chromomycin A3; D008926:Plicamycin