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

Pereira, Rodrigo Machado; Ferreira-Silva, Guilherme Alvaro; Pivatto, Marcos; Santos, Luciana de Avila [UNESP]; Bolzani, Vanderlan da Silva [UNESP]; Chagas de Paula, Daniela Aparecida; Oliveira, Jaqueline Carvalho de; Viegas Junior, Claudio; Ionta, Marisa

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

Arquivos

WOS000369879700010.pdf (1005.36 KB)

Data

2016-03-01

Autores

Pereira, Rodrigo Machado

Ferreira-Silva, Guilherme Alvaro

Pivatto, Marcos

Santos, Luciana de Avila

Bolzani, Vanderlan da Silva

Chagas de Paula, Daniela Aparecida

Oliveira, Jaqueline Carvalho de

Viegas Junior, Claudio

Ionta, Marisa

Editor

Elsevier B.V.

Tipo

Artigo

Direito de acesso

Acesso aberto

Resumo

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 ERIC 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. (C) 2015 Elsevier Ltd. All rights reserved.