Pachymic acid inhibits cell growth and modulates arachidonic acid metabolism in nonsmall cell lung cancer A549 cells

Abstract

Aberrant arachidonic acid (AA) metabolism has been involved in inflammation and carcinogenesis. The key enzymes in AA metabolism such as cytosolic phospholipase A2 (cPLA 2 ) and cyclooxygenase-2 (COX-2) have been implicated in the development and progression of many human cancers, including lung cancer. Hence, the blockade of these enzymes may suppress promotion and survival of human cancer cells. We and others have shown that a natural triterpenoid, pachymic acid (PA), can exhibit antiinflammatory and anticancer properties; however, its potential mechanism has not been fully clarified. In this study, we examined the effect of PA on the proliferation of human nonsmall cell lung cancer A549 cells. Furthermore, we investigated the influences of nontoxic levels of PA on AA metabolism. Additionally, the cellular events and signal transduction pathways influenced by PA were also examined. Our results showed that PA (1) inhibited anchorage-dependent and -independent A549 growth in a concentrationdependent manner, (2) induced apoptosis and disrupted mitochondrial membrane potential in A549 cells, and at nonlethal levels, (3) decreased IL-1b-induced activation of cPLA 2 and COX-2, (4) suppressed IL-1b-induced activation of mitogen-activated protein kinases (MAPKs), and (5) inhibited IL-1b-stimulated nuclear factor kappa B (NF-kB) signaling pathways. We speculate that inhibition of AA metabolism by PA is mediated in part by its inhibition of MAPKs and NF-kB signaling pathways. Our study reveals that, apart from its cytotoxic effect, PA has the chemopreventive potential by reducing production of eicosanoids from AA metabolism.

Synthesis, biological activity screening and molecular modeling study of acylaminoacetamide derivatives

“…A549 cell line is a powerful tool to study the effect of different conditions on COX-2 expression due to its low or undetectable level of COX-2 isoenzyme expression (Mitchell et al, 1994;Sievers et al, 2005). Moreover, it is also known that the inflammatory cytokine, interleukin-1b (IL-1b), strongly upregulates COX-2 expression and PGE 2 synthesis in A549 cells (Ling et al, 2010). Since IL-1b-stimulated A549 cells do not express COX-1, it has been suggested that the upregulation of the PGE 2 is mainly dependent on COX-2 enzyme activity (Koeberle et al, 2008).…”

“…Since IL-1b-stimulated A549 cells do not express COX-1, it has been suggested that the upregulation of the PGE 2 is mainly dependent on COX-2 enzyme activity (Koeberle et al, 2008). Therefore, in our experimental model, the expression of COX-2 has been triggered in A549 cells with IL-1b treatment, and the effect of the title compounds on upregulated COX-2 protein expression was determined by Western Blotting experiment (Ling et al, 2010;Jiang et al, 2004). Similarly, inhibitory effects of title compounds on PGE 2 production (pg/mL) in IL-1b-stimulated A549 cell lines were performed by enzyme immunoassay procedure (EIA) (Ling et al, 2010).…”

“…Therefore, in our experimental model, the expression of COX-2 has been triggered in A549 cells with IL-1b treatment, and the effect of the title compounds on upregulated COX-2 protein expression was determined by Western Blotting experiment (Ling et al, 2010;Jiang et al, 2004). Similarly, inhibitory effects of title compounds on PGE 2 production (pg/mL) in IL-1b-stimulated A549 cell lines were performed by enzyme immunoassay procedure (EIA) (Ling et al, 2010). In this method, the elevated PGE 2 level in IL-1b-activated A549 cell lines has been linked to the induced COX-2 isoenzyme expression (Huang et al, 1998).…”

Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7

“…Poria cocos (also known as Wolfiporia extensa) is a medicinal mushroom in the Polyporaceae family that grows in pine trees and its sclerotium is widely used in traditional Asian medicine for its sedative, diuretic, digestive and tonic effects (6)(7)(8). Although the anticancer activity of polysaccharides extracted from P. cocos is associated with the stimulation of immune response and these polysaccharides significantly enhance immunopotentiation (9), triterpenes isolated from P. cocos have a direct inhibitory effect on cancer cells through a variety of mechanisms including inhibition of cell proliferation, induction of apoptosis and suppression of invasive behavior (10)(11)(12)(13)(14)(15)(16). However the effect of triterpenes from P. cocos against pancreatic cancer remains to be evaluated and the mechanism determined.…”

Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7

“…Poria cocos (also known as Wolfiporia extensa ) is a medicinal mushroom in the Polyporaceae family that grows in pine trees and its sclerotium is widely used in traditional Asian medicine for its sedative, diuretic, digestive and tonic effects (6–8). Although the anticancer activity of polysaccharides extracted from P. cocos is associated with the stimulation of immune response and these polysaccharides significantly enhance immunopotentiation (9), triterpenes isolated from P. cocos have a direct inhibitory effect on cancer cells through a variety of mechanisms including inhibition of cell proliferation, induction of apoptosis and suppression of invasive behavior (10–16). However the effect of triterpenes from P. cocos against pancreatic cancer remains to be evaluated and the mechanism determined.…”