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. (March 2016)

• Record Type: Journal Article
• Authors: Pereira, Rodrigo Machado; Ferreira-Silva, Guilherme Álvaro; Pivatto, Marcos; Santos, Luciana de Ávila; Bolzani, Vanderlan da Silva; Chagas de Paula, Daniela Aparecida; Oliveira, Jaqueline Carvalho de; Viegas Júnior, Cláudio; Ionta, Marisa
• Is Part Of: Toxicology in vitro. Volume 31(2016)
• Page Start: 86
• Page End: 92
• Publication Date: 2016-03
• Subjects: Hepatocellular carcinoma -- Cell cycle arrest -- (−)-Cassine -- (−)-Spectaline -- Piperidine alkaloids -- Senna spectabilis; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2015.11.018
• Languages: English
• ISSNs: 0887-2333

Abstract

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 alkaloids1 /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 alkaloids1 /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. Highlights: (−)-Cassine/(−)-Spectaline alkaloid mixture inhibits cell proliferation in hepatocellular carcinoma cell line. Antiproliferative activity of (−)-cassine/(−)-spectaline alkaloids is associated to cell cycle arrest in G1/S transition. (−)-Cassine/(−)-Spectaline alkaloids are effective in modulating cyclin D expression. ERK activation is inhibited in HepG2 cells treated with (−)-cassine/(−)-spectaline alkaloids.