Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of microsomal stearoyl-CoA desaturation, NADH-cytochrome b5 reductase, NADH-cytochrome c reductase, and the content of cytochrome b5 were similar in livers of normal and host rats. On the other hand, stearoyl-CoA desaturation activity was absent in Novikoff hepatoma. The activities of NADH-cytochrome b5 and NADH-cytochrome c reductases in the hepatoma microsomes were 4.8% and 2.2%, respectively, of those in normal liver. Furthermore, in hepatoma microsomes, cytochrome b5 was absent. An active stearoyl-CoA desaturation was reconstituted only on addition of both cytochrome b5 and the terminal desaturase enzyme to the hepatoma microsomes. These results indicated that a complete absence of cytochrome b5 and terminal desaturase is responsible for the lack of stearoyl-CoA desaturation in Novikoff hepatoma microsomes.
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PMID:Stearoyl-coenzyme A desaturase activity in Novikoff hepatoma. 3 26

The microsomal stearoyl-CoA desaturase system was examined in both the Morris hepatoma 7288CTC, maintained in the host Buffalo strain rat, and the Morris hepatoma 7288C, maintained in tissue culture. In vitro examination shows the stearoyl-CoA desaturase system to be similar in the 2 tissues. Both show extremely low overall stearoyl-CoA desaturase activity, having 4% and 8% of normal liver values respectively. Examination of the electron transport system showed both tissues have decreased electron transport components cytochrome b5 and cytochrome b5 reductase. Particularly noticeable were the extremely low levels of cytochrome b5 (2% compared with normal liver). Microsomes from both tissues showed a decreased ability to reduce an artificial electron acceptor, cytochrome c. With the low levels of cytochrome b5 observed in these tissues, the low levels of overall desaturase activity may be caused by lack of terminal enzyme, lack of sufficient cytochrome b5, or both. Analysis of the stearoyl-CoA desaturase system in cultured hepatoma cells suggests that these cells are similar to the host-grown tumor in this respect and may be used as a model in further examinations of the stearoyl-CoA desaturase system.
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PMID:Analysis of the stearoyl-CoA desaturase system in the Morris hepatoma 7288C and 7288CTC. 614 13

The effect of Semecarpus anacardium Linn. nut milk extract on host detoxification system in aflatoxin B(1) induced hepatocellular carcinoma, which is a vital mechanism in cancer treatment, was studied in male albino rats. Oral administration of nut extract (200 mg kg(-1)body weight per day for 14 days) is found to be highly effective in inducing phase I and phase II biotransformation enzymes. The obtained results have shown an overall decrease of liver microsomal cytochrome P450, cytochrome b5, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, and aniline hydroxylase with a subsequent decrease of phase II enzymes, glutathione-S-transferase and UDP-glucuronyl transferase in cancer-bearing animals. The Semecarpus anacardium nut extract affords anticancer activity by enhancing both phase I and phase II enzymes to near normal levels. We propose that, much of the anticarcinogenic potency of Semecarpus anacardium nut extract on aflatoxin B(1)-induced hepatocarcinogenesis is mediated through the induction of hepatic biotransformation enzymes.
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PMID:Potency of Semecarpus anacardium Linn. nut milk extract against aflatoxin B(1)-induced hepatocarcinogenesis: reflection on microsomal biotransformation enzymes. 1088 46

The environmental carcinogen benzo[a]pyrene (BaP) is presumed to exert its genotoxic effects after metabolic activation by cytochrome P450 (CYP) enzymes. However, studies using the Hepatic Reductase Null (HRN) mouse model, in which cytochrome P450 oxidoreductase (POR), the electron donor to CYP enzymes, is deleted specifically in hepatocytes, have shown that loss of hepatic POR-mediated CYP function leads to greater BaP-DNA adduct formation in livers of these mice than in wild-type (WT) mice. Here, we used CRISPR/Cas9 technology to knockout (KO) POR expression in mouse hepatoma Hepa1c1c7 cells to create an in vitro model that can mimic the HRN mouse model. Western blotting confirmed the deletion of POR in POR KO Hepa1c1c7 cells whereas expression of other components of the mixed-function oxidase system including cytochrome b5 (Cyb5) and NADH:cytochrome b5 reductase (which can also serve as electron donors to CYP enzymes), and CYP1A1 was similar in BaP-exposed WT and POR KO Hepa1c1c7 cells. BaP exposure caused cytotoxicity in WT Hepa1c1c7 cells but not in POR KO Hepa1c1c7 cells. In contrast, CYP-catalysed BaP-DNA adduct levels were ~10-fold higher in POR KO Hepa1c1c7 cells than in WT Hepa1c1c7 cells, in concordance with the presence of higher levels of BaP metabolite (e.g. BaP-7,8-dihydrodiol) in the medium of cultured BaP-exposed POR KO Hepa1c1c7 cells. As was seen in the HRN mouse model, these results suggest that Cyb5 contributes to the bioactivation of BaP in POR KO Hepa1c1c7 cells. These results indicate that CYP enzymes may play a more important role in the detoxication of BaP, as opposed to its bioactivation.
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PMID:Deletion of cytochrome P450 oxidoreductase enhances metabolism and DNA adduct formation of benzo[a]pyrene in Hepa1c1c7 cells. 3161 22