Effects of indirubin and isatin on cell viability, mutagenicity, genotoxicity and BAX/ERCC1 gene expression

Made available in DSpace on 2018-11-26T17:39:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-07-25 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood. Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN-and ISA-induced expression of ERCC1 or BAX genes. Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24 h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72 h) tests after treatment with IRN (0.1 to 200 mu M) or ISA (0.5 to 50 mu M). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24 h) by gavage (50, 100 and 150 mg/kg determined from the LD50 - 1 g/kg b.w.) and submitted to comet assay in vivo. Results: IRN reduced the viability of CHO-K1 (24 h; 5 to 200 mu M) and HeLa cells (10 to 200 mu M), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10 mu M; HeLa: 5 and 10 mu M). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24 h) at all doses tested. IRN (100 and 150 mg/kg) also induced genotoxicity in vivo (4 h). Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations. Univ Estadual Londrina, Ctr Biol Sci, Dept Gen Biol, Celso Garcia Cid Rd,PR 445 Km 380, BR-86057970 Londrina, Parana, Brazil Sao Paulo State Univ, Araraquara Inst Chem, Araraquara, Brazil Sao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil Sao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, Brazil Yale Sch Med, Abraham Ribicoff Res Facil, New Haven, CT USA Sao Paulo State Univ, Araraquara Inst Chem, Araraquara, Brazil Sao Paulo State Univ, Araraquara Fac Pharmaceut Sci, Dept Biol Sci, Araraquara, Brazil Sao Paulo State Univ, Expt Campus Paulista Coast, Sao Vicente, Brazil