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

Toxicol In Vitro. 2016 Mar:31:86-92. doi: 10.1016/j.tiv.2015.11.018. Epub 2015 Nov 23.

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.

Keywords: (−)-Cassine; (−)-Spectaline; Cell cycle arrest; Hepatocellular carcinoma; Piperidine alkaloids; Senna spectabilis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cyclin D1 / metabolism
  • Down-Regulation
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Flowers
  • Humans
  • Ketones / pharmacology*
  • Piperidines / pharmacology*
  • Senna Plant

Substances

  • Antineoplastic Agents
  • Ketones
  • Piperidines
  • spectaline
  • Cyclin D1
  • cassine
  • Extracellular Signal-Regulated MAP Kinases