title: Cytotoxicity of the beta-carboline alkaloids harmine and harmaline in human cell assays in vitro.
abstract: beta-Carboline alkaloids are natural products widely distributed in plants and also found in alcoholic beverages, well-cooked foods and tobacco smoke. Various authors have reported genotoxic activities of several carboline in prokaryotic and eukaryotic cells that have been attributed to their abilities to intercalate into DNA. But studies on the genotoxic and on the cytotoxic potencies in human cells in vitro are not found in the literature. In the present study the toxicities of one full aromatic beta-carboline alkaloid (harmine) and one dihydro-beta-carboline alkaloid (harmaline) were evaluated by means of two in vitro human cell assays: the cytochalasin-B blocked micronucleus (CBMN) assay and the viability/colony formation assay with four different human cultured non-transformed (CCD18Lu) and transformed (HeLa, C33A and SW480) cells. Neither alkaloid was able to induce micronuclei levels above that of control levels in a wide range of doses tested; although, harmine at the highest concentrations assayed induced apoptotic as well as necrotic cells. Harmine produced a good viability of all cell lines assayed (control and tumor) while harmaline significantly reduced the viability of transformed and non-transformed cell lines in a dose-dependent manner. Harmine displayed a dose-dependent inhibitory effect on cell proliferation against all human carcinoma cells, but the SW480 transformed cell line showed a higher sensitivity. These results suggested that harmine was identified as a useful inhibitor of tumor development.
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad Nacional Autónoma de México, 04510 Coyoacán, México, DF, Mexico.
authors.forename: Judith
authors.initials: J
authors.lastname: Jiménez
authors.forename: Leticia
authors.initials: L
authors.lastname: Riverón-Negrete
authors.forename: Fikrat
authors.initials: F
authors.lastname: Abdullaev
authors.forename: Javier
authors.initials: J
authors.lastname: Espinosa-Aguirre
authors.forename: Rosario
authors.initials: R
authors.lastname: Rodríguez-Arnaiz
mesh_terms: D000328:Adult; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D005260:Female; D006246:Harmaline / Q000633:toxicity*; D006247:Harmine / Q000633:toxicity*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015162:Micronucleus Tests
chemical_list: D000697:Central Nervous System Stimulants; D006247:Harmine; D006246:Harmaline