ubiquinone and Carcinoma--Hepatocellular

It has been reported that higher levels of oxidative stress and inflammation play a key role in the progression of hepatocellular carcinoma (HCC) after surgery. Coenzyme Q10 is an endogenous lipid-soluble antioxidant. To date, no intervention study has investigated coenzyme Q10 supplementation in HCC patients after surgery. The purpose of this study was to investigate oxidative stress, antioxidant enzymes activity, and inflammation levels in HCC patients after surgery following administration of coenzyme Q10 (300 mg/day).. This study was designed as a single-blinded, randomized, parallel, placebo-controlled study. Patients who were diagnosed with primary HCC (n = 41) and were randomly assign to a placebo (n = 20) or coenzyme Q10 (300 mg/day, n = 21) group after surgery. The intervention lasted for 12 weeks. Plasma coenzyme Q10, vitamin E, oxidative stress antioxidant enzymes activity and inflammatory markers levels were measured.. The oxidative stress (p = 0.04) and inflammatory markers (hs-CRP and IL-6, p < 0.01) levels were significantly decreased, and the antioxidant enzymes activity was significantly increased (p < 0.01) after 12 weeks of coenzyme Q10 supplementation. In addition, the coenzyme Q10 level was significantly negatively correlated with the oxidative stress (p = 0.01), and positively correlated with antioxidant enzymes activity (SOD, p = 0.01; CAT, p < 0.05; GPx, p = 0.04) and vitamin E level (p = 0.01) after supplementation.. In conclusion, we demonstrated that a dose of 300 mg/d of coenzyme Q10 supplementation significantly increased the antioxidant capacity and reduced the oxidative stress and inflammation levels in HCC patients after surgery.. Clinical Trials.gov Identifier: NCT01964001.

Topics: Aged; Antioxidants; Biomarkers; Body Mass Index; Body Weight; C-Reactive Protein; Carcinoma, Hepatocellular; Catalase; Dietary Supplements; Female; Humans; Inflammation; Interleukin-6; Linear Models; Liver Neoplasms; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Single-Blind Method; Superoxide Dismutase; Ubiquinone; Vitamin E

The current study aimed to test the profile of serum lipids, phospholipase D (PLD) activity, and CD59 expression pattern in rat hepatocellular carcinoma (HCC) after therapeutic treatment with Coenzyme Q10 (CoQ10). Three rat groups were allocated as normal control, untreated HCC, and treated HCC (HCC + CoQ10). The levels of serum α-fetoprotein (AFP) and tumour necrosis factor (TNF)-α were assessed using enzyme-linked immunosorbent assay (ELISA), while proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry (IHC). Serum lipids, classical (CH50), and alternative (APH50) pathways of complement activation, the liver cell HMG-CoA reductase (HMGCR), and PLD activities were assayed colorimetrically. The protein expression of CD59, scavenger receptor class B type 1 (SRB1), B cell lymphoma-2 (Bcl2), and cleaved Caspase-3 (Casp-3) were detected using western blotting, while the level of serum CD59 (sCD59) was assessed using dot-blot. CoQ10 reduced the cell proliferation, histological alterations, and the levels of AFP and TNF-α but increased lipids, CH50, and sCD59 in serum. In the liver cell, CoQ10 decreased and increased PLD and HMGCR enzyme activities, respectively. In addition, reduction of liver CD59, Bcl2, and SRB1 vs increased cleaved Casp-3 expressions was observed. Statistical correlation indicated an inverse relationship between CH50 and each of CD59 expression and PLD activity after treatment with CoQ10. In conclusion, CoQ10 could protect against rat HCC through increased lipids and the reduction of CD59 expression and PLD activity. SIGNIFICANCE OF THE STUDY: To our knowledge, this study is the first to describe the attenuating effect of antitumour natural product like Coenzyme Q10 (CoQ10) via the reduction of CD59 expression and phospholipase D (PLD) activity. This illustrates the important role of CD59 and PLD in relation to lipids in cancer prevention.

Topics: Animals; Carcinogenesis; Carcinoma, Hepatocellular; CD59 Antigens; Gene Expression Regulation, Neoplastic; Lipid Metabolism; Liver Neoplasms, Experimental; Male; Neoplasm Proteins; Phospholipase D; Rats; Ubiquinone

Topics: Acyltransferases; Adaptor Proteins, Signal Transducing; Antineoplastic Agents, Phytogenic; Antrodia; Autophagy; beta Catenin; Carcinoma, Hepatocellular; Hep G2 Cells; Humans; Liver Neoplasms; Signal Transduction; TOR Serine-Threonine Kinases; Transcription Factors; Ubiquinone; Wnt Proteins; YAP-Signaling Proteins

(1) Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer deaths worldwide, and surgical resection is the main treatment for HCC. To date, no published study has examined the status of coenzyme Q10 in patients with HCC after surgery. Thus, the purpose of this study was to investigate the correlations between the level of coenzyme Q10, oxidative stress, and inflammation in patients with HCC after surgery; (2) Methods: 71 primary HCC patients were recruited. Levels of coenzyme Q10, vitamin E, oxidative stress (malondialdehyde), antioxidant enzymes activity (superoxidase dismutase, catalase, and glutathione peroxidase), and inflammatory markers (high sensitivity C-reactive protein; tumor necrosis factor-α; and interleukin-6) were measured; (3) Results: Patients with HCC had a significantly lower levels of coenzyme Q10 (

Topics: Adult; Aged; Aged, 80 and over; Aspartate Aminotransferases; Blood Glucose; C-Reactive Protein; Carcinoma, Hepatocellular; Creatinine; Glutathione Peroxidase; Humans; Inflammation; Interleukin-6; Linear Models; Liver Neoplasms; Malondialdehyde; Middle Aged; Oxidative Stress; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Ubiquinone; Vitamin E; Young Adult

Mitochondria are a major source of reactive oxygen species (ROS) and are also the target of cellular ROS. ROS damage to mitochondria leads to dysfunction that further enhances the production of mitochondrial ROS. This feed-forward vicious cycle between mitochondria and ROS induces cell death. Within a few minutes of radiation exposure, NADPH oxidase is activated to elevate the ROS level. Activated NADPH oxidase might induce the feed-forward cycle of mitochondria and this is a possible mechanism for cancer cell death induced by heavy ion irradiation. We found that after 4 Gy of (12) C(6+) ion radiation of HepG2 cells, the NADPH oxidase membrane subunit gp91(phox) was not involved in enzyme activation through increased expression; however, the subunit p47(phox) was involved in activation by being translocated to the membrane. (12) C(6+) ion radiation clearly decreased the ΔΨm of HepG2 cells, increasing mitochondrial DNA damage and inducing cell death. Pretreatment with apocynin (APO, an NADPH oxidase inhibitor) effectively prevented the ΔΨm decrease, mitochondrial DNA damage, and cell death induced by radiation. However, these protective effects were not observed with APO treatment after irradiation exposure. These data demonstrated that NADPH oxidase activation was an initiator in mitochondrial damage. Once mitochondria entered the feed-forward cycle, cell fate was no longer controlled by NADPH oxidase. Only antioxidants that targeted mitochondria such as MitoQ could break the cycle and release cells from death.

Topics: Adaptor Proteins, Signal Transducing; Antioxidants; Apoptosis; Carcinoma, Hepatocellular; Enzyme Activation; Heavy Ion Radiotherapy; Hep G2 Cells; Humans; Liver Neoplasms; Membrane Glycoproteins; Mitochondria, Liver; NADPH Oxidase 2; NADPH Oxidases; Organophosphorus Compounds; Oxidation-Reduction; Reactive Oxygen Species; Ubiquinone

The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis.

Topics: alpha-Fetoproteins; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Carcinoma, Hepatocellular; Cyclooxygenase 2; Glutathione; Lipid Peroxidation; Liver Neoplasms, Experimental; Male; Malondialdehyde; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Trichloroacetic Acid; Tumor Necrosis Factor-alpha; Ubiquinone

5'AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are two serine/threonine protein kinases responsible for cellular energy homeostasis and translational control, respectively. Evidence suggests that these two kniases are potential targets for cancer chemotherapy against hepatocellular carcinoma (HCC). Antroquinonol that is isolated from Antrodia camphorate, a well-known Traditional Chinese Medicine for treatment of liver diseases, displayed effective anticancer activity against both HBV DNA-positive and -negative HCC cell lines. The rank order of potency against HCCs is HepG2>HepG2.2.15>Mahlavu>PLC/PRF/5>SK-Hep1>Hep3B. Antroquinonol completely abolished cell-cycle progression released from double-thymidine-block synchronization and caused a subsequent apoptosis. The data were supported by down-regulation and reduced nuclear translocation of G1-regulator proteins, including cyclin D1, cyclin E, Cdk4 and Cdk2. Further analysis showed that the mRNA expressions of the G1-regulator proteins were not modified by antroquinonol, indicating an inhibition of translational but not transcriptional levels. Antroquinonol induced the assembly of tuberous sclerosis complex (TSC)-1/TSC2, leading to the blockade of cellular protein synthesis through inhibition of protein phosphorylation including mTOR (Ser(2448)), p70(S6K) (Thr(421)/Ser(424) and Thr(389)) and 4E-BP1 (Thr(37)/Thr(46) and Thr(70)). Furthermore, the AMPK activity was elevated by antroquinonol. Compound C, a selective AMPK inhibitor, significantly reversed antroquinonol-mediated effects suggesting the crucial role of AMPK. Besides, the loss of mitochondrial membrane potential and depletion of mitochondrial content indicated the mitochondrial stress caused by antroquinonol. In summary, the data suggest that antroquinonol displays anticancer activity against HCCs through AMPK activation and inhibition of mTOR translational pathway, leading to G1 arrest of the cell-cycle and subsequent cell apoptosis.

Topics: Adenylate Kinase; Base Sequence; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; DNA Primers; Flow Cytometry; Humans; Liver Neoplasms; Phosphorylation; Protein Kinases; Reverse Transcriptase Polymerase Chain Reaction; TOR Serine-Threonine Kinases; Ubiquinone

Ubiquinone (coenzyme Q; CoQ) is the only lipophilic antioxidant that is endogenously synthesized by all organisms. CoQ biosynthesis is determined in vitro by supplying a radiolabeled precursor and, after lipid extraction and CoQ separation by thin-layer chromatography or high-performance liquid chromatography, the radioactivity present in the sample is quantified. In the rapid and simple method described here, we avoid the use of organic solvents by supplying 4-hydroxy-[U-14C]benzoate as radiolabeled precursor and precipitating CoQ with trichloroacetic acid (TCA). After TCA precipitation, all radioactivity was present in the precipitate and CoQ was the only radiolabeled molecule detected. The radioactive material was then solubilized with NaOH and quantified in a scintillation counter.

Topics: Carbon Radioisotopes; Carcinoma, Hepatocellular; Humans; Parabens; Tumor Cells, Cultured; Ubiquinone

Coenzyme Q (CoQ) is an essential component of the mitochondrial electron transport chain and serves as an electron donor and acceptor in mitochondrial energy-linked respiration. CoQ1 was shown to prevent ROS formation and cell death in complex 1 inhibited cells. Low concentrations of capsaicin like CoQ1 inhibited ROS formation but CoQ1 was more effective at restoring the mitochondrial membrane potential collapse caused by complex 1 inhibitors such as rotenone. At low concentrations, capsaicin acts as a CoQ mimic by protecting against rotenone induced ROS formation and mitochondrial membrane potential collapse. Lipid peroxidation in isolated rat hepatocytes induced by cumene hydroperoxide and chloroacetaldehyde was also prevented. At higher concentrations, capsaicin and CoQ1 became cytotoxic. Hep G2 cells were more susceptible than hepatocytes. The cytotoxic mechanism for both capsaicin and CoQ1 was shown to involve a collapse of the mitochondrial membrane potential, however, only capsaicin caused ROS formation. The capsaicin side chain was required for capsaicin induced cytotoxicity. The anticancer properties of CoQ1 and capsaicin should prove useful for inducing tumor cell apoptosis.

Topics: Animals; Antineoplastic Agents; Capsaicin; Carcinoma, Hepatocellular; Cell Death; Cell Division; Cytoprotection; Hepatocytes; Humans; Lipid Peroxidation; Liver Neoplasms; Male; Membrane Potentials; Mitochondria, Liver; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Rotenone; Structure-Activity Relationship; Tumor Cells, Cultured; Ubiquinone

To assess the degree of oxidative stress, we measured plasma ubiquinone-10 percentage (%CoQ-10) in total amounts of ubiquinone-10 in patients with chronic active hepatitis, liver cirrhosis, and hepatocellular carcinoma, and in age-matched control subjects, %CoQ-10 values were 12.9 +/- 10.3 (n = 28), 10.6 +/- 6.8 (n = 28), 18.9 +/- 11.1 (n = 20), and 6.4 +/- 3.3 (n = 16), respectively, showing a significant increase in oxidative stress in patient groups as compared to control subjects. There were no differences in total amounts of ubiquinone-10 and ubiquinol-10 among the four groups. We next measured %CoQ-10 in plasmas obtained from nine patients treated with percutaneous transluminal coronary angioplasty (PTCA). Plasmas were collected when hospitalized, and at the time (0, 4, 8, 12, 16, and 20 hr, and 1, 2, 3, 4, and 7 days) after the PTCA. %CoQ-10 values before and right after PTCA were 9.9 +/- 2.8 and 11.4 +/- 2.0, respectively, reached a maximum (20-45) at 1 or 2 days later, and decreased to 7.9 +/- 2.7 at 7 days after PTCA, indicating an increase in oxidative stress in patients during coronary reperfusion.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Ascorbic Acid; beta Carotene; Bilirubin; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Reference Values; Ubiquinone; Uric Acid; Vitamin E

The present study was undertaken to investigate possible effects of dietary iron during the progression step in hepatocarcinogenesis.. Two experiments were performed, in which preneoplastic foci were produced in rat liver using the Solt & Farber protocol, with diethylnitrosamine as initiator and partial hepatectomy + 2-acetylaminofluorene as promoter. Two weeks after promotion, animals were fed 1.25-2.5% dietary carbonyl iron or a control diet until sacrifice. In the first experiment, animals were killed at different time points when they developed an abdominal mass in combination with weight loss. In the second experiment, animals were sacrificed 45 weeks post-promotion. Liver tumours were counted and histologically graded. Tumour levels of ubiquinone-9 and alpha-tocopherol were determined with HPLC, and labelling and apoptotic indices calculated using immunohistochemistry. The number and area of glutathione S-transferase 7,7 (GST-7,7)-positive foci were determined.. In experiment number 1, survival and tumour differentiation were similar in iron-treated animals and controls. In the second experiment, iron-treated rats had an increased number of GST-7,7-positive foci compared to controls. Number and size of carcinomas were similar between the groups, whereas tumour differentiation was higher in rats exposed to iron. Cell proliferation, apoptosis and concentrations of alpha-tocopherol in tumours were not altered by iron. The ratio of reduced/oxidized ubiquinone-9 was decreased in tumours from iron-treated animals.. In this model, dietary iron overload resulted in an increased number of preneoplastic foci but did not enhance the progression of these into hepatocellular carcinomas. Iron decreased the ratio of reduced/oxidized ubiquinone-9 in tumours, indicating that neoplastic liver cells utilize intracellular ubiquinones as a defense mechanism against iron-induced oxidative stress.

Topics: 2-Acetylaminofluorene; Animals; Apoptosis; Carcinogens; Carcinoma, Hepatocellular; Cell Division; Chromatography, High Pressure Liquid; Diethylnitrosamine; Disease Progression; Glutathione Transferase; Hemochromatosis; Iron; Iron, Dietary; Liver; Liver Neoplasms, Experimental; Male; Oxidative Stress; Rats; Rats, Wistar; Ubiquinone; Vitamin E

We have applied our method for the simultaneous detection of plasma ubiquinol-10 (reduced form) and ubiquinone-10 (oxidized form) (S. Yamashita and Y. Yamamoto, Anal. Biochem. 250, 66-73, 1997) to plasmas of normal subjects (n = 16) and patients with chronic active hepatitis (n = 28), liver cirrhosis (n = 16), and hepatocellular carcinoma (n = 20) to evaluate the pressure of oxidative stress in these patients. The average ubiquinone-10 percentages (+/- S.D.) in total ubiquinone-10 and ubiquinol-10 in the four groups were 6.4 +/- 3.3, 12.9 +/- 10.3, 10.6 +/- 6.8, and 18.9 +/- 11.1, respectively, indicating a significant increase in ubiquinone-10 percentage in patient groups in comparison to normal subjects. These results and a significant decrease in the plasma ascorbate level in patient groups indicate that oxidative stress is evident after the onset of hepatitis and the subsequent cirrhosis and liver cancer.

Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Carcinoma, Hepatocellular; Carotenoids; Cholesterol; Cholesterol Esters; Female; Hepatitis, Chronic; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Lycopene; Male; Middle Aged; Oxidative Stress; Ubiquinone; Vitamin E

Oxidative stress is defined as a disturbance in the prooxidant-antioxidant balance in favor of the former and has been suggested to be a relevant factor in aging as well as in different pathological conditions, such as heart attack, diabetes, and cancer. Ubiquinol is very sensitive against oxygen radicals and gives ubiquinone as an oxidation product. Therefore, the ratio of ubiquinol to ubiquinone should be a good marker of oxidative stress because of its definition. A method for the simultaneous detection of ubiquinol-10 and ubiquinone-10 in human plasma is described. Heparinized human plasma was mixed with 5 volumes of methanol and 10 volumes of hexane. After vigorous shaking and centrifugation, the hexane phase (5 microliters) was injected immediately and directly on to reverse-phase HPLC equipped with an on-line reduction column and an electrochemical detector in order to avoid the oxidation of ubiquinol to ubiquinone. It was found that the ratio of ubiquinol-10 to ubiquinone-10 was about 95/5 in human plasma from healthy donors. A significant increase in the oxidized form (ubiquinone-10) content was observed in plasmas of patients with hepatitis, cirrhosis, and hepatoma when compared with normal subjects, suggesting increased oxidative stress in these patients.

Topics: Biomarkers; Carcinoma, Hepatocellular; Chromatography, High Pressure Liquid; Coenzymes; Electrochemistry; Hepatitis; Hexanes; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Solvents; Ubiquinone; Vitamin E

Ubiquinol-10 (CoQ10H2) is present in human low density lipoproteins (LDL) where it contributes significantly to the antioxidant defenses against radical-mediated oxidative damage. As CoQ10H2 becomes oxidized to ubiquinone-10 (CoQ10) during the earliest stages of in vitro oxidation of LDL, we investigated a possible cellular recycling of oxidized CoQ10H2, adding CoQ10 or its ambiphilic, short-chain analogue ubiquinone-1 (CoQ1), to cells that are exposed to LDL in vivo. Whole blood, isolated red blood cells and human hepatoma Hep G2 cells (used as a model of hepatocytes) rapidly and efficiently reduced added CoQ1 to ubiquinol-1 (CoQ1H2) detectable outside the cells. In whole blood the same steady-state level of CoQ1H2 was reached whether an equimolar amount of CoQ1 or CoQ1H2 was added. Red cell membranes also showed some reducing activity, whereas CoQ1 added to human blood plasma remained largely in its oxidized form. Cell- and membrane-mediated reduction of CoQ1 was enhanced by NADH, FAD, or human plasma. In comparison to this rapid reduction of extracellular CoQ1, formation of CoQ10H2 from CoQ10 incorporated into human LDL by red blood and Hep G2 cells was slow. Our results show that although human blood cells and Hep G2 cells are endowed with a highly reducing activity for CoQ1, the natural CoQ10 does not appear to represent an efficient substrate for this activity.

Topics: Adult; Blood Cells; Carcinoma, Hepatocellular; Humans; Kinetics; Lipoproteins, LDL; Liver; Oxidation-Reduction; Tumor Cells, Cultured; Ubiquinone

Surgical samples of human hepatic tissue were analysed morphologically and biochemically and highly differentiated hepatomas were compared with two control groups: morphologically normal liver tissue surrounding the tumour, and tissue from normal livers. In tumour homogenates cholesterol levels were more than twice, ubiquinone levels about half and the concentration of free dolichol about 10% of the control value. The levels of dolichyl phosphate were basically similar, whereas the phospholipid level was slightly lower in the tumours. In microsomes isolated from hepatomas, the level of cholesterol was about 30% higher than the control value. HMG-CoA reductase activity in microsomes isolated from hepatomas was elevated almost 100% in comparison to control. In hepatomas, no major alterations in the compositions of dolichol or dolichyl phosphate could be observed. The relative amounts of alpha-saturated and alpha-unsaturated polyprenols were also basically unaltered in hepatomas. Liver samples were incubated with 3H-mevalonic acid and radioactivity was monitored in polyprenols. With control tissue, incorporation was considerably higher in alpha-unsaturated polyprenols than in their alpha-saturated counterparts. In the tumours the rates of incorporation into both polyprenol fractions were much lower, although still higher in the alpha-unsaturated fraction. Labelling of polyisoprenols containing 19 isoprene residues was higher than that of 20 residues. The pattern of labelling in the polyisoprenyl-P fraction was similar. In hepatomas the incorporation into cholesterol and ubiquinone-10 was about 100% higher and 50% lower respectively compared with control tissue. The results in this study of hepatomas indicate that the levels of various lipids may be influenced not only by the regulatory enzyme HMG-CoA reductase, but also by other enzymes catalysing reactions subsequent to this regulatory point. It is also suggested that levels of cholesterol, ubiquinone and dolichol may be regulated independently subsequent to the branch point at farnesylpyrophosphate.

Topics: Carcinoma, Hepatocellular; Cholesterol; Dolichol Phosphates; Dolichols; Humans; Liver Neoplasms; Terpenes; Ubiquinone

The levels of cholesterol, ubiquinone and dolichol and the polyprenol composition of dolichol in human hepatocellular carcinomas (hepatomas) with different degrees of differentiation were analyzed and compared with healthy liver tissue. Dolichols were also analyzed in liver metastases. The total level of cholesterol was increased, while the levels of dolichol and ubiquinone were decreased in all hepatomas, but no correlation between these levels and the degree of differentiation of the hepatomas could be observed. The level of dolichol decreased more in the hepatomas than in the liver metastases. The dolichol fraction from hepatomas with a low degree of differentiation contained higher relative amounts of short polyisoprenols (D17) and slightly lower relative amounts of D21 compared with healthy liver tissue, metastatic liver tumors or hepatomas with a high degree of differentiation. The significance of the lipid values found in the different groups is discussed.

Topics: Adult; Carcinoma, Hepatocellular; Cell Membrane; Cholesterol; Dolichols; Humans; Liver Neoplasms; Middle Aged; Terpenes; Ubiquinone

The lipid composition of human hepatocellular carcinomas was examined. The level of dolichol in the tumours was decreased compared to control tissue, whereas the concentration of dolichyl phosphate did not exhibit any major change. A decrease in the amount of dolichyl ester was also observed. The pattern of individual polyisoprenoids in the free dolichol pool was changed in several carcinomas with a relative increase in the shorter dolichols. The isoprenol composition in the dolichyl ester and phosphate fractions of tumours were basically similar to those of controls. alpha-Unsaturated polyisoprenols are present in control livers at a level of 3% of the total free polyisoprenoid fraction, while this value was increased in the tumours. Similar to dolichol, the amount of ubiquinone was also decreased. The content of cholesterol was increased, while the fatty acid pattern of the dolichyl esters showed minor alterations. These modifications in lipid content indicate different mechanisms for the regulation of dolichol and dolichyl phosphate concentrations. The high levels of sterols in contrast to the low polyisoprenol content suggests interference with the regulation of the mevalonate pathway, which is the common biosynthetic route for cholesterol, ubiquinone and dolichol.

Topics: Adult; Aged; Carcinoma, Hepatocellular; Cholesterol; Dolichol Phosphates; Dolichols; Fatty Acids; Humans; Liver Neoplasms; Middle Aged; Ubiquinone

The lipid compositions of homogenates and microsomal fractions derived from surgical samples of highly differentiated human hepatoma, morphologically normal regions outside the tumours and from normal livers were analysed. A few enzyme activities were also assayed. Hepatoma microsomes demonstrated considerably lowered levels of cytochromes P-450 and b5. Hepatoma homogenates exhibited increased levels of cholesterol, normal amounts of dolichyl-P and slightly lowered levels of total phospholipid. The levels of dolichol, dolichol ester and ubiquinone in hepatoma homogenates were prominently decreased. In tumour microsomes the levels of cholesterol and dolichyl phosphate were increased considerably while the levels of phospholipid and dolichol were lowered. The phospholipid composition of tumour homogenates was roughly similar to that of control tissue. In tumour microsomes the relative amounts of phosphatidylserine and phosphatidylinositol were about 30% decreased, whereas the major phospholipids showed minor increases in amount. The rate and pattern of incorporation of [3H]glycerol into individual phospholipids in liver slices from control and hepatoma tissue did not differ to any larger extent. The fatty acid composition of tumour homogenates exhibited minor differences in comparison to the control with the greatest changes in the sphingomyelin fraction. In hepatoma microsomes the fatty acid compositions of the major phospholipids were altered moderately, with evident decreases in the relative amounts of the long-chain polyunsaturated fatty acids. In hepatoma homogenates the fatty acid composition of dolichol esters differed only slightly from the control pattern. These results indicate that the major disturbance in the lipid metabolism of highly differentiated hepatomas is localized to the mevalonate pathway, thus affecting mainly the levels of cholesterol, dolichol and ubiquinone.

Topics: Carcinoma, Hepatocellular; Cholesterol; Cytochrome b Group; Cytochrome P-450 Enzyme System; Cytochromes b5; Dolichols; Fatty Acids; Humans; Lipids; Liver; Liver Neoplasms; Microsomes, Liver; Middle Aged; Phospholipids; Ubiquinone

Topics: Carcinoma, Hepatocellular; Cholesterol; Diterpenes; Dolichols; Humans; Hydroxymethylglutaryl CoA Reductases; Liver; Liver Neoplasms; Microsomes; Microsomes, Liver; Ubiquinone

Topics: Abdominal Muscles; Aged; Animals; Ascites; Carcinoma; Carcinoma, Hepatocellular; Chromatography, Paper; Female; Humans; Intestinal Neoplasms; Intestine, Large; Liver; Liver Neoplasms; Male; Middle Aged; Mitochondria; Mitochondria, Liver; Neoplasm Metastasis; Neoplasms; Neoplasms, Experimental; Oxidoreductases; Stomach Neoplasms; Ubiquinone

Topics: Animals; Ascites; Carcinoma, Hepatocellular; Coenzymes; Electron Transport Complex II; Liver Neoplasms; Liver Neoplasms, Experimental; Mechlorethamine; Naphthoquinones; Neoplasms, Experimental; Oxidoreductases; Rats; Succinate Dehydrogenase; Succinates; Succinic Acid; Tetrazolium Salts; Ubiquinone; Vitamin K; Vitamin K 3

Topics: Biochemical Phenomena; Carcinoma, Hepatocellular; Coenzymes; Liver; Liver Neoplasms; Ubiquinone