An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident.
The juice of the entire fresh herb and infusion of dried sample of Murdannia bracteata are consumed to treat liver cancer and diabetes in Malaysia. However, no scientific evidence of these bioactivities has been reported.
Goniothalamin is a biologically active styrylpyrone derivative isolated from various Goniothalamus species. The ability of goniothalamin to induce apoptosis via caspase-3 activation against hepatoblastoma (HepG2) and normal liver cells (Chang cells) was studied using morphological and biochemical evaluations. HepG2 and Chang cells were treated with goniothalamin for 72 h and analysed by TUNEL and Annexin-V/PI staining. Furthermore, the post-mitochondrial caspase-3 was quantified using ELISA. In view of our results, goniothalamin induced apoptosis on treated cells via alteration of cellular membrane integrity and cleavage of DNA. On the other hand, post-mitochondrial caspase-3 activity was significantly elevated in HepG2 cells treated with goniothalamin after 72 h. These findings suggest that goniothalamin induced apoptosis on HepG2 liver cancer cells via induction of caspase-3 with less sensitivity on the cell line of Chang cells.
This study was undertaken to see if liver function tests (LFT) served a worthwhile purpose in the investigation of hepatocellular carcinoma (HCC). Sera from 80 HCC, 76 benign liver disease (BLD) and 152 healthy adult (HA) subjects were assayed for alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase and lactate dehydrogenase, bilirubin and albumin. Cut-off values were determined from the HA. ALP, GGT, AST and albumin were abnormal in about 90% of the HCC. With the exception of bilirubin, the LFT were abnormal more frequently in HCC than in chronic hepatitis and cirrhosis, the conditions which preceed it. Raised ALP in the presence of normal bilirubin was more often a feature of HCC than BLD although this relationship was not statistically significant. It seems unlikely that LFT serve a useful function in HCC.
To determine whether tumor marker pi glutathione transferase (GST-pi) is expressed in hepatocellular carcinoma (HCC) and other chronic liver diseases and to compare its expression with that of alpha-fetoprotein (AFP).
Glucoraphanin is the main glucosinolate found in broccoli and other cruciferous vegetables (Brassicaceae). The objective of the study was to evaluate whether glucoraphanin and its breakdown product sulforaphane, are potent modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro. The glucosinolate glucoraphanin was isolated from cruciferous vegetables and exposed to human hepatoma cell line HepG2 at various concentrations (0-25 μM) for 24 hours. Glucoraphanin at higher concentration (25 μM) decreased dealkylation of methoxyresorufin, a marker for cytochrome P4501 activity; supplementation of the incubation medium with myrosinase (0.018 U), the enzyme that converts glucosinolate to its corresponding isothiocyanate, showed minimal induction in this enzyme activity at concentration 10 μM. Quinone reductase and glutathione S-transferase activities were unaffected by this glucosinolate; however, supplementation of the incubation medium with myrosinase elevated quinone reductase activity. It may be inferred that the breakdown product of glucoraphanin, in this case sulforaphane, is superior than its precursor in modulating carcinogen- metabolising enzyme systems in vitro and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.
Early development of liver cancer is usually asymptomatic. The overall survival rate of patients is relatively low due to late diagnosis, despite hepatocellular carcinoma being a common diagnosis. The high mortality rate of liver cancer was due to its overactivated cellular mitochondrial activities, namely thioredoxin reductase enzymatic activities and its downstream activation of nuclear factor kappa B (NF-κB) signaling pathways for cancer cell migration. Our previous study on this candidate compound on A2780 ovarian cancer cells and MCF-7 breast cancer cells, through modulation of cell-cycle checkpoints and respective targeted apoptosis pathways. The current study used HepG2 hepatocellular carcinoma cell lines as a representative in vitro liver cancer cell model. The half maximal inhibitory concentration (IC50) value was obtained via incubation of PTZ compound for 24 h yield of 37.03 μM, whereby it was three-fold more potent than the standard control tested, cisplatin (109.23 μM). The subsequent application of IC50 dosage of PTZ onto HepG2 cells illustrated a growth-static effect via activation of S-phase cell-cycle checkpoints, immediately followed by regulation of apoptosis. Increased cellular concentration of reactive oxygen species eventually generated oxidative damages on mitochondria, hence resulting in the release of cytochrome c protein and suppression of TrxR enzymatic activity, in conjunction with the suppression on invasion of cancer cells via Matrigel invasion chamber. In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research.
The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by determining the activities of gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), glutathione S-transferases (GSTs), and glutathione (GSH) levels in blood and liver. Twenty-eight male 7- to 8-wk-old Rattus norwegicus rats, weighing 120-160 g, were used in this study. The rats were divided into four treatment groups: a control group on a basal diet, a group fed a basal diet supplemented with tocotrienol (30 mg/kg food), a group treated with DEN/AAF, and a group treated with DEN/AAF and fed a diet supplemented with tocotrienol (30 mg/kg food). Blood was collected monthly, and GGT, ALP, and GSH levels were determined. The rats were killed after 9 mo, and the livers were examined morphologically. Grayish white nodules (2/liver) were found in all the DEN/AAF-treated rats (n = 10), but only one of the rats treated with DEN/AAF and supplemented with tocotrienol (n = 6) had liver nodules. A significant increase in the level of blood and liver GSH, ALP, and GGT activities was observed in the DEN/AAF-treated rats. Liver GSTs were similarly increased with DEN/AAF treatment. Tocotrienol supplementation attenuated the impact of the carcinogens in the rats.
This study was conducted to investigate the potential of bambangan (Mangifera pajang) fruit extracts in the protection against oxidative damage caused by tert-butyl hydroperoxide in the human hepatocellular HepG2 cell line. Proteins which might be involved in the cytoprotective mechanism were investigated using western blotting technique. Quercetin was used as a positive control. The results showed that only the kernel extract of M. pajang and quercetin displayed cytoprotective activity in HepG2 cells, with EC(50) values of 1.2 and 5.3μg/ml, respectively. Expression of quinone reductase, glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by quercetin, suggesting their involvement in the cytoprotective activity of quercetin. However, expressions of only glutathione reductase and methionine sulfoxide reductase A proteins were significantly up-regulated by the kernel extract, again suggesting their involvement in the cytoprotective activity of bambangan kernel extract. Future study is needed to investigate the involvement of other cytoprotective proteins in the cytoprotection mechanism.