Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present paper, the regulation of 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase, acylcoenzyme A cholesterol acyltransferase (ACAT) and low-density lipoprotein (LDL) binding was studied in the human colon cancer carcinoma cell line Caco-2. LDL down-regulated HMG-CoA reductase activity in a dose-dependent fashion to a minimum of 28% of control at 200 micrograms/ml and LDL binding to 52% of control. The activity of ACAT was stimulated by LDL. High-density lipoprotein 3 (HDL3) increased HMG-CoA reductase activity, whereas cholesteryl ester formation was slightly decreased. Inhibition of the endogenous cholesterol biosynthesis by mevinolin increased both LDL binding and activity of HMG-CoA reductase. This effect was reversed by the addition of mevalonolactone but not by LDL. It is concluded that regulation of HMG-CoA reductase and LDL binding is subject to the availability of non-sterol products of mevalonic acid and of exogenous cholesterol. ACAT is regulated mainly by the level of its substrate cholesterol.
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PMID:Regulation of cholesterol metabolism and low-density lipoprotein binding in human intestinal Caco-2 cells. 163 21

Gastrin-releasing peptide (GRP) and its receptor (GRPR) are aberrantly up-regulated in colon cancer. When expressed, they act as morphogens, retaining tumor cells in a better differentiated state and retarding metastasis. To identify targets activated in response to GRPR signaling we studied Caco-2 and HT-29 cells, colon cancer cell lines that expresses GRPR as a function of confluence. Total cell protein was extracted from pre-confluent cells (expressing GRP/GRPR) cultured in serum-free media in the presence or absence of GRPR-specific antagonist; as well as from confluent cells that do not express GRPR. Overall, we identified 5 proteins that are specifically down-regulated after GRP/GRPR expression: Bach2, creatine kinase B, p47, and two that could not be identified; and 6 proteins that are up-regulated: gephyrin, HSP70, HP1, ICAM-1, ACAT, and one that could not be identified. These findings suggest that the mechanism(s) by which GRP/GRPR mediate its morphogenic effects in colon cancer involve the actions of a number of hitherto unappreciated proteins.
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PMID:Consequence of gastrin-releasing peptide receptor activation in a human colon cancer cell line: a proteomic approach. 1673 97

Undesirable side effects remain a significant challenge in cancer chemotherapy. Here we report a strategy for cancer-selective chemotherapy by blocking acyl-CoA cholesterol acyltransferase-1 (ACAT-1)-mediated cholesterol esterification. To efficiently block cholesterol esterification in cancer in vivo, we developed a systemically injectable nanoformulation of avasimibe (a potent ACAT-1 inhibitor), called avasimin. In cell lines of human prostate, pancreatic, lung, and colon cancer, avasimin significantly reduced cholesteryl ester storage in lipid droplets and elevated intracellular free cholesterol levels, which led to apoptosis and suppression of proliferation. In xenograft models of prostate cancer and colon cancer, intravenous administration of avasimin caused the concentration of avasimibe in tumors to be 4-fold higher than the IC50 value. Systemic treatment of avasimin notably suppressed tumor growth in mice and extended the length of survival time. No adverse effects of avasimin to normal cells and organs were observed. Together, this study provides an effective approach for selective cancer chemotherapy by targeting altered cholesterol metabolism of cancer cells.
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PMID:Avasimibe encapsulated in human serum albumin blocks cholesterol esterification for selective cancer treatment. 2566 6