title: Alkaloids derived from flowers of Senna spectabilis, (-)-cassine and (-)-spectaline, have antiproliferative activity on HepG2 cells for inducing cell cycle arrest in G1/S transition through ERK inactivation and downregulation of cyclin D1 expression.
abstract: Cancer is one of the most critical problems of public health in the world and one of the main challenges for medicine in this century. Unfortunately, most patients are diagnosed at advanced stage, when the treatment options are palliative. Consequently, the search for novel therapeutic options is imperative. In the context, the plants represent an important source for discovering of novel compounds with pharmacological potential including antineoplastic agents. Herein, we aimed to investigate in vitro antiproliferative and cytotoxic potentials of an alkaloid mixture derived from Senna spectabilis, (−)-cassine (1) and (−)-spectaline (2). These alkaloids reduced cell viability in a concentration-dependent manner of six tumor cell lines. From initial screening, HepG2 cells were selected for further investigations. We show that alkaloids 1/2 have an important antiproliferative activity on HepG2 cells due to their ability in inducing cell cycle arrest in G1/S transition. This effect was associated to ERK inactivation and down-regulation of cyclin D1 expression. In addition, we evidenced a disruption of the microfilaments and microtubules in a consequence of the treatment. Taken together, the data showed by the first time that alkaloids 1/2 strongly inhibit cell proliferation of hepatocellular carcinoma cells. Therefore, they represent promise antitumor compounds against liver cancer and should be considered for further anticancer in vivo studies.
authors.affiliation: Institute of Biomedical Sciences, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, zip code 37130-000 Alfenas, MG, Brazil.
authors.forename: Rodrigo Machado
authors.initials: RM
authors.lastname: Pereira
authors.affiliation: Institute of Biomedical Sciences, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, zip code 37130-000 Alfenas, MG, Brazil.
authors.forename: Guilherme Álvaro
authors.initials: GÁ
authors.lastname: Ferreira-Silva
authors.affiliation: Nucleus of Research in Natural Products (NuPPeN), Institute of Chemistry, Federal 'University of Uberlândia, Avenida João Naves de Ávila, 2121, zip code 38408-144 Uberlândia, MG, Brazil.
authors.forename: Marcos
authors.initials: M
authors.lastname: Pivatto
authors.affiliation: Institute of Chemistry, State University of São Paulo, Rua Francisco Degni s/n, zip code 14801-970 Araraquara, SP, Brazil.
authors.forename: Luciana de Ávila
authors.initials: Lde Á
authors.lastname: Santos
authors.affiliation: Institute of Chemistry, State University of São Paulo, Rua Francisco Degni s/n, zip code 14801-970 Araraquara, SP, Brazil.
authors.forename: Vanderlan da Silva
authors.initials: Vda S
authors.lastname: Bolzani
authors.affiliation: Laboratory of Phytochemistry and Medicinal Chemistry (LFQM), Institute of Chemistry, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, zip code 37130-000 Alfenas, MG, Brazil.
authors.forename: Daniela Aparecida
authors.initials: DA
authors.lastname: Chagas de Paula
authors.affiliation: Institute of Natural Science, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, zip code 37130-000 Alfenas, MG, Brazil.
authors.forename: Jaqueline Carvalho de
authors.initials: JC
authors.lastname: Oliveira
authors.affiliation: Laboratory of Research on Medicinal Chemistry (PeQuiM), Institute of Chemistry, Federal University of Alfenas, Av. Jovino Fernandes Sales, 2600, zip code 37130-000 Alfenas, MG, Brazil.
authors.forename: Cláudio
authors.initials: C
authors.lastname: Viegas Júnior
authors.affiliation: Institute of Biomedical Sciences, Federal University of Alfenas, Rua Gabriel Monteiro da Silva, 700, zip code 37130-000 Alfenas, MG, Brazil. Electronic address: marisaionta@gmail.com.
authors.forename: Marisa
authors.initials: M
authors.lastname: Ionta
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D035264:Flowers; D006801:Humans; D007659:Ketones / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D029846:Senna Plant
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D010880:Piperidines; C480880:spectaline; D019938:Cyclin D1; C426663:cassine; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: (−)-Cassine; (−)-Spectaline; Cell cycle arrest; Hepatocellular carcinoma; Piperidine alkaloids; Senna spectabilis