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.

The Chemical Profile of Senna velutina Leaves and Their Antioxidant and Cytotoxic Effects

“…The search for new molecules with therapeutic properties, including antioxidant and anticarcinogenic activities, is facilitated by the vast biodiversity and bioprospecting potential in Brazil. Senna genus has been used in Brazilian folk medicine for its antioxidant, antimicrobial [ 11 ], anti-inflammatory [ 12 ], antidiabetic [ 13 ], and antitumor [ 14 ] activities, among other uses.…”

Novel Therapeutic Uses of Legume Crops in Southern South America

“…There are also several reports [46] of populations of S. spectabilis from Brazil, whose fruits and flowers have pharmacological effects (analgesic and anti-inflammatory) due to the presence of more than 20 piperine and piperidine alkaloid compounds. It has been also presented important compounds report in leishmanicidal activity [47] and the strongly inhibit cell proliferation of hepatocellular carcinoma cells in alkaloids derived from flowers (in vitro antiproliferative and cytotoxic potentials of alkaloid mixture); if they represent promise antitumor compounds against liver cancer and should be considered for further anticancer in vivo studies [48].…”

Convergent Synthesis of <i>trans</i>-2,6-Disubstituted Piperidine Alkaloid, (−)-<i>iso</i>-6-Spectaline by Palladium-Catalyzed Cyclization

“…1). These alkaloids are reported to exert a variety of biological effects including DNA-modifying, 2) antibacterial, 3) anti-candidal, 4) and HepG2 cell anti-proliferative activities. 5) In addition, they have been reported to inhibit the growth of human-infective Trypanosoma species 6) and the activity of acetylcholinesterase 7) ; however the structure-activity relationship, especially for the stereo-structures of the substituents on the piperidine scaffold, has not been examined.…”