Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1864663 (HCC)
 2,985 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclooxygenase-2 (COX-2), a rate limiting step in arachidonic acid cascade, plays a key role in the biosynthesis of prostaglandin E2 (PGE2) upon inflammatory stimuli, growth factors, hormones and other cellular stresses. Overproduction of PGE2 stimulates proliferation of various cancer cells, confers resistance to apoptosis and favors metastasis and angiogenesis. The steady-state level of PGE2 is maintained by interplay between the biosynthetic pathway including COX and PGE2 synthases and the catabolic pathways involving nicotinamide adenine dinucleotide (NAD(+))-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH). 15-PGDH is a crucial enzyme responsible for the biological inactivation of PGE2. Adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory factors used. COX-2 is induced in hepatocytes after partial hepatectomy (PH), in animal models of cirrhosis, in human hepatoma cell lines, in human HCC and after HBV and HCV infection. However, no data are available regarding 15-PGDH expression in HCC. Our results show that 15-PGDH is downregulated in human hepatoma cells with a high COX-2 expression, in chemical and genetic murine models of HCC and in human HCC biopsies. Moreover, 15-PGDH expression is suppressed by EGF (epidermal growth factor) and HGF (hepatocyte growth factor) mainly involving PI3K (phosphatidylinositol-3-kinase), ERK (extracellular signal-regulated kinase) and p38MAPK (mitogen-activated protein kinase) activation. Conversely, ectopic expression of 15-PGDH induces apoptosis in hepatoma cells and decreases the growth of hepatoma cells in nude mice whereas the silencing of 15-PGDH increases the tumor formation. These data suggest a potential therapeutic application of 15-PGDH in HCC.
...
PMID:Regulation of 15-hydroxyprostaglandin dehydrogenase expression in hepatocellular carcinoma. 2395 7

The antitumor effect of hydroxysafflor yellow A (HSYA), an active ingredient of the herb Carthamus tinctorius L. (Asteraceae) (safflower), was investigated in the current work. Researches of HSYA on vasculogenesis inhibition, along with the related molecular mechanisms, including the expression of MMP-2, MMP-9, and p38MAPK (COX-2, ATF-2, p-p38MAPK, and p38MAPK) signaling pathway in H22 tumor-bearing mice or HepG2 cells were performed. The animal experiments proved the level of MMP-2 and MMP-9 in H22-transplanted tumor tissue in mice markedly decreased by HSYA, and results both in vivo and in vitro confirmed that COX-2 expression was reduced significantly via p38MAPK|ATF-2 signaling pathway. According to the outcomes, HSYA suppressed p38MAPK phosphorylation in a concentration-dependent manner, while exerting no effect on the total p38MAPK protein expression. It was also showed that suppression of p38 activation by SB203580 decreased the HepG2 cell viability, proliferation, and migration, wherein HSYA exhibited a similar effect. Furthermore, Western blot analysis on caspase-3 and cleaved-caspase-3 revealed that HSYA could induce apoptosis of HepG2 cells. These findings provided experimental evidences that HSYA might be a promising anticancer agent for HCC.
 ...
PMID:Hydroxysafflor yellow A suppresses angiogenesis of hepatocellular carcinoma through inhibition of p38 MAPK phosphorylation. 3055 34