title: In vitro antiproliferative effects of the indole alkaloid vallesiachotamine on human melanoma cells.
abstract: In course of a screening for small molecules presenting potential anticancer properties, a known monoterpene indole alkaloid named vallesiachotamine was isolated from the leaves of Palicourea rigida (Rubiaceae) collected in the Brazilian Cerrado. The structure was determined by spectroscopic methods, mainly 1D- and 2D-NMR and its biological activities were investigated on cultured human (SK-MEL-37) melanoma cells. In vitro cytotoxicity was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory concentration (IC(50)) was 14.7 ± 1.2 μM for 24 h of drug exposure. Flow cytometry analysis revealed that vallesiachotamine induced G0/G1 arrest and increased the proportion of sub-G1 hypodiploid cells (at 11 μM and 22 μM) and this effect was not dependent on time of incubation. At these concentrations, a typical ladder was observed by agarose gel electrophoresis of the extracted DNA. Treatment of cells with 50 μM vallesiachotamine for 24 h caused extensive cytotoxicity and necrosis. Our results demonstrated that the indole alkaloid vallesiachotamine exhibited important cytotoxicity toward human melanoma cells and that apoptosis and necrosis might be responsible for the observed events.
authors.affiliation: Laboratory of Cellular Biochemistry, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO 74001-970, Brazil.
authors.forename: Paula R O
authors.initials: PR
authors.lastname: Soares
authors.forename: Pollyana Laurindo
authors.initials: PL
authors.lastname: de Oliveira
authors.forename: Cecília M A
authors.initials: CM
authors.lastname: de Oliveira
authors.forename: Lucilia
authors.initials: L
authors.lastname: Kato
authors.forename: Lídia Andreu
authors.initials: LA
authors.lastname: Guillo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma / Q000473:pathology*; D009336:Necrosis; D018515:Plant Leaves; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D019666:Rubiaceae / Q000737:chemistry; D012878:Skin Neoplasms / Q000473:pathology*; D013997:Time Factors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; C573958:vallesiachotamine