Cytotoxicity and genotoxicity of ingenamine G isolated from the Brazilian marine sponge Pachychalina alcaloidifera.
Marine sponges belonging to the order Haplosclerida are one of the more prolific sources of new natural products possessing various biological activities. The present study examined the cytotoxic and genotoxic potential of ingenamine G, an alkaloid isolated from the Brazilian marine sponge Pachychalina alcaloidifera. Ingenamine G displayed a moderate cytotoxic activity against human proliferating lymphocytes evaluated by the MTT assay (IC(50) 15 microg/mL). The hemolytic assay showed that ingenamine G cytotoxic activity was not related to membrane disruption. The comet assay and chromosome aberration analysis were applied to determine the genotoxic and clastogenic potential of ingenamine G, respectively. Cultured human lymphocytes were treated with 5, 10, 15 and 20 microg/mL of ingenamine G during the G(1), G(1)/S, S (pulses of 1 and 6 h), and G(2) phases of the cell cycle. All tested concentrations were cytotoxic, reduced significantly the mitotic index, and were clastogenic in all phases of the cell cycle, especially in S phase. While an increase in DNA-strand breaks was observed starting with the concentration corresponding to the IC(50). The presence of genotoxicity and polyploidy during interphase and mitosis, respectively, suggests that ingenamine G at high concentrations is clastogenic and indirectly affects the construction of mitotic fuse.
Cavalcanti
Bruno Coêlho
BC
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, CP 3157, CEP 60430-270, Fortaleza, CE, Brazil.
Sombra
Carla Maria Lima
CM
de Oliveira
Jaine H H L
JH
Berlinck
Roberto Gomes de Souza
RG
de Moraes
Manoel Odorico
MO
Pessoa
Claudia
C
D000293:Adolescent; D000328:Adult; D000470:Alkaloids / Q000302:isolation & purification / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000139:chemically induced; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005562:Formazans / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000302:isolation & purification / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D011161:Porifera / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000378:metabolism
D000470:Alkaloids; D005562:Formazans; D006576:Heterocyclic Compounds, 4 or More Rings; D009153:Mutagens; D013778:Tetrazolium Salts; C493695:ingenamine G; C079782:MTT formazan