Cheng Hui, Su Jing-Jing, Peng Jian-Ya, Wang Mei, Wang Xun-Cui, Yan Feng-Gen, Wang Xiao-Shan, Li Qing-Lin
Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Traditional Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei, 230038, China.
J Asian Nat Prod Res. 2011 Oct;13(11):993-1002. doi: 10.1080/10286020.2011.605062. Epub 2011 Oct 19.
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.
藤黄是藤黄科植物藤黄分泌的一种干燥树脂，藤黄酸（GNA）是藤黄的主要活性成分之一。我们之前已经证明了GNA在A549细胞中的抗癌活性，并指出了其在抗癌治疗中的潜在作用。先前的研究报道，GNA可诱导多种癌细胞系凋亡，并在裸鼠体内异种移植模型中抑制A549肿瘤生长。然而，GNA的抗癌机制尚未得到充分研究。在本文中，我们研究了GNA诱导的凋亡是否关键地由p38丝裂原活化蛋白激酶（MAPK）途径介导。我们的研究结果表明，GNA可诱导凋亡、抑制增殖、下调p38和MAPK的表达、增加caspase-9、caspase-3的活化以及细胞色素c的释放。此外，使用p38 MAPK的三磷酸腺苷竞争性抑制剂SB203580抑制p-p38的表达，实验结果表明其可能促进GNA诱导的凋亡的发生。综上所述，这些结果表明p38 MAPK级联的上调可能是GNA诱导凋亡激活的原因。
