title: Risk Assessment via Metabolism and Cell Growth Inhibition in a HepG2/C3A Cell Line Upon Treatment with Arpadol and its Active Component Harpagoside.
abstract: Harpagophytum procumbens (Hp) has been used as antiinflammatory and analgesic agent for the treatment of rheumatic diseases. The principal active component of Hp is harpagoside (HA). We tested the toxicity of this new therapeutic agent in a hepatic cell line (HepG2/C3A). Hp was found to be cytotoxic, and HA was found to decrease the number of cells in S phase, increase the number of cells in G2/M phase and induce apoptosis. Neither Hp nor HA was genotoxic. The expression of CDK6 and CTP3A4 was reduced by Hp, and both HA and Hp caused a significant reduction of CYP1A2 and CYP3A4 expression. It is possible that the cytotoxicity caused by HA and Hp does not involve transcriptional regulation of the cyclins and CDKs tested but is instead related to the inhibition of metabolism. This is evidenced by the results of an MTT assay and changes in the expression of genes related to drug metabolism, leading to cell death. Indeed, the cells exhibited decreased proliferation upon exposure to Hp and HA. The data show that treatment with either Hp or HA can be cytotoxic, and this should be taken into consideration when balancing the risks and benefits of treatments for rheumatic diseases. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Departamento de Biologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil.
authors.forename: Bruna Isabela
authors.initials: BI
authors.lastname: Biazi
authors.affiliation: Departamento de Biologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil.
authors.forename: Gláucia Fernanda Rocha
authors.initials: GF
authors.lastname: D'Epiro
authors.affiliation: Departamento de Biologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil.
authors.forename: Thalita Alves
authors.initials: TA
authors.lastname: Zanetti
authors.affiliation: Departamento de Biologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil.
authors.forename: Marcelo Tempesta
authors.initials: MT
authors.lastname: de Oliveira
authors.affiliation: Departamento de Patologia, Faculdade de Medicina, Universidade Estadual Paulista, Av. Prof. Montenegro, Distrito de Rubião Junior, Botucatu, São Paulo, Brazil.
authors.forename: Lucia Regina
authors.initials: LR
authors.lastname: Ribeiro
authors.affiliation: Departamento de Biologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina-UEL, Rodovia Celso Garcia Cid, Pr 445 Km 380, Londrina, Paraná, Brazil.
authors.forename: Mário Sérgio
authors.initials: MS
authors.lastname: Mantovani
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006027:Glycosides / Q000494:pharmacology / Q000633:toxicity*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000633:toxicity*; D031684:Harpagophytum / Q000737:chemistry; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology / Q000633:toxicity*; D011714:Pyrans / Q000494:pharmacology / Q000633:toxicity*; D018570:Risk Assessment; D018675:Toxicity Tests
chemical_list: D006027:Glycosides; D006131:Growth Inhibitors; D010936:Plant Extracts; D011714:Pyrans; C000618350:arpadol; C033249:harpagoside
keywords: Devil's claw; cell cycle; cytotoxicity; harpagoside; proliferation