Gambogenic acid inhibits proliferation of A549 cells through apoptosis inducing through up-regulation of the p38 MAPK cascade

Abstract

Gamboge is a dry resin secreted from Garcinia hanburryi, and gambogenic acid (GNA) is one of the main active compounds of gamboge. We have previously demonstrated the anticancer activity of GNA in A549 cells and pointed out its potential effects in anticancer therapies. Previous studies reported that GNA induced apoptosis in many cancer cell lines and inhibited A549 tumor growth in xenograft of nude mice in vivo. However, the anticancer mechanism of GNA has still not been well studied. In this paper, we have investigated whether GNA-induced apoptosis is critically mediated by the p38 mitogen-activated protein kinase (MAPK) pathway. Our findings revealed that GNA could induce apoptosis, inhibit proliferation, down-regulate the expression of p38 and MAPK, increase the activations of caspase-9, caspase-3, and cytochrome c release. Furthermore, using SB203580, an adenosine triphosphate-competitive inhibitor of p38 MAPK, inhibit the expression of p-p38 and the experimental results show that it may promote the occurrence of apoptosis induced by GNA. Taken together, these results suggested that up-regulation of the p38 MAPK cascade may account for the activation of GNA-induced apoptosis.

<p>Traditional Chinese medicine-combination therapies utilizing nanotechnology-based targeted delivery systems: a new strategy for antitumor treatment</p>

“…glioblastoma cells, 49 breast cancer, 50 lung cancer 51 Gambogenic acid is associated with inhibition of proliferation of A549 cells by apoptosis induction and cell-cycle arrest, 48,52,53 and Medulloblastoma, 60 lung cancer cells, 61 blood cancer cells, colon cancer cells, breast cancer cells, brain cancer cells, ovary cancer cells, kidney cancer cells, prostate cancer cells 62,63 Triptolide can inhibit cell proliferation and arrest the cell cycle, 64 increase LC3α expression levels, 65 and inhibit the PI3K-Akt-mTOR pathway. while eRK1/2 is activated, autophagy of cell death is induced.…”

A novel glyceryl monoolein-bearing cubosomes for gambogenic acid: Preparation, cytotoxicity and intracellular uptake

“…Afterward, apoptotic cell was identified by double supravital staining with recombinant fluorescein isothiocyanate (FITC)-conjugated Annexin-V and PI, using the Annexin V-FITC apoptosis detection kit (Becton Dickinson, Canaan, CT, USA) according to manufacturer's instructions (Cheng et al, 2011). In short, SMMC-7721 cells were harvested by gently adding trypsin and rinsed twice with cold PBS.…”

Gambogenic acid induces proteasomal degradation of CIP2A and sensitizes hepatocellular carcinoma to anticancer agents

“…Gambogenic acid (GEA) is another active component of gamboge which exhibits cytotoxicity and anti-inflammatory activity (19,20). The molecular mechanisms that underlie the effects of GEA include induction of cell cycle arrest (21,22), apoptosis (21,(23)(24)(25)(26)(27), autophagy (22,28), necroptosis (29) and chemosensitivity (29,30). Herein, we demonstrated that GEA induced rapid proteasome-mediated degradation of CIP2A.…”