tretinoin and Hepatoblastoma

This study inquired into the role of retinoic acid in lipoprotein metabolism.. We observed the effect of retinoic acid on the secretion of apolipoproteins A I, A II, C III, B100 and E by cultured HepG2 cells. The apolipoprotiens contents in culture media were measured by radioimmunodiffusion assay (RID) kits developed by our research laboratory. 20-fold lyophilizely condensed culture media were used for the assays.. Retinoic acid increased the secretion of apoA I, B100, C III and A II, and it inhibited the secretion of apoE. The effect of retinoic acid was strengthened in a dose-dependent manner. When the concentration of retinoic acid in cultured media was 2 x 10(-4) mol/l, the secretion of apoA I, A II, B100 and C III increased by 14.3% (P < 0.01), 23.8% (P < 0.05), 16.1% (P < 0.01) and 47.6% (P < 0.01) respectively, and the secretion of apoE decreased by 37.2% (P < 0.01).. These findings indicate that retinoic acid does not have a general effect on apolipoprotein secretion in HepG2 cells.

Topics: Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins; Apolipoproteins B; Apolipoproteins C; Apolipoproteins E; Hepatoblastoma; Humans; Liver Neoplasms; Tretinoin; Tumor Cells, Cultured

To investigate the regulatory mechanism of multidrug resistance(MDR) caused by all-trans retinoic acid (ATRA).. ATRA and IL-4 were used to treat human hepatoblastoma cell line (HepG2) cells. The proliferative activity, synthesis of alpha fetal protein (AFP), and cell cycle distribution of tumor cells were observed to evaluate the degree of cell differentiation. Flow cytometry and in situ hybridization were used to determine the expressing levels of p53, bcl-2, P-glycoprotein (P-gp) and c-jun and c-myc mRNA. MTT assay was used to evaluate the sensitivity of the tumor cells to chemotherapeutic agents.. Both ATRA and IL-4 could induce the differentiation of HepG2 cells. ATRA treatment of the tumor cells led to drug resistance in chemotherapy (resistant factors: 1.6-3.1), and IL-4 increased the sensitivity of the tumor cells to antineoplasic drugs (reversal index: 4-17). The level of P-gp expression in ATRA-treated cells was increased from 54.2% +/- 8.6% up to 98.5% +/- 1.4% (P < 0.01), but IL-4 markedly inhibited expression of P-gp down to 25.4% +/- 7.3% (P < 0.01). Both ATRA and IL-4 treatment could down-regulate c-jun and c-myc mRAN expressions. The level of p53 and bcl-2 expression could be up- or down-regulated by IL-4 treatment but they were unaffected by ATRA treatment.. Degree of cell differentiation and level of c-jun and c-myc mRNA expression might not be related to change in drug sensitivity by inducing differentiation of HepG2 cells with ATRA and IL-4. Increased expression of P-gp caused by ATRA might be one of the factors up-regulating MDR. p53 (or bcl-2) might be involved in regulating the sensitivity of antineoplastic drugs by inducing differentiation.

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Differentiation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Gene Expression; Genes, jun; Genes, myc; Hepatoblastoma; Humans; Interleukin-4; Liver Neoplasms; Proto-Oncogene Proteins c-bcl-2; RNA, Messenger; Tretinoin; Tumor Cells, Cultured; Tumor Suppressor Protein p53

A high serum concentration of lipoprotein(a) [Lp(a)] is a significant and independent risk factor for cardiovascular disease. We examined the effects of agents on the transcriptional activity of the apolipoprotein(a) [apo(a)] gene promoter and determined whether drugs identified by this assay would affect the serum concentration of Lp(a) in vivo. All-trans-retinoic acid (ATRA) and interleukin-6 increased the transcriptional activity of the apo(a) gene promoter 2.1- and 2.5-fold, respectively, whereas danazol reduced activity to 76% of the control value. Triiodothyronine had no effect on transcriptional activity. Treatment of two acute promyelocytic leukemia patients with ATRA induced maximal 2.7- and 3.2-fold increases in serum Lp(a) concentrations, respectively. Thus, the in vitro luciferase assay system is capable of identifying agents that affect the serum concentration of Lp(a) and thus may prove beneficial in the screening of new drugs for treatment of individuals with high serum Lp(a) concentrations.

Topics: Adult; Apolipoproteins; Apoprotein(a); Base Sequence; Cell Line; Danazol; DNA; DNA Primers; Female; Gene Expression Regulation, Neoplastic; Genes, Reporter; Hepatoblastoma; Humans; Interleukin-6; Kinetics; Leukemia, Promyelocytic, Acute; Lipoprotein(a); Liver Neoplasms; Luciferases; Male; Middle Aged; Promoter Regions, Genetic; Recombinant Fusion Proteins; Transcription, Genetic; Transfection; Tretinoin; Triiodothyronine; Tumor Cells, Cultured; Vitamin E

Transglutaminase is a calcium-dependent enzyme that catalyzes an amine incorporation and a cross-linking of proteins. Intracellular transglutaminase is induced when human promyelocytic leukemia HL-60 cells are treated with retinoic acid and human hepatoblastoma HepG2 cells, with interleukin-6. To find whether the intracellular reaction catalyzed by transglutaminase increased when the enzyme is induced in these cells, the transglutaminase-catalyzed incorporation of 14C-labeled methylamine into cellular proteins was measured. The incorporation level of the labeled methylamine into proteins of HL-60 and HepG2 cells did not increase after the transglutaminase had been induced. The presence of the calcium ionophore A23187 did not affect these results. These findings suggested that even after the enzyme induction the catalytic action of intracellular transglutaminase is maintained at a constant level in these cells by unknown regulatory mechanism(s).

Topics: Calcimycin; Catalysis; Enzyme Induction; Hepatoblastoma; HL-60 Cells; Humans; Interleukin-6; Ionophores; Leukemia, Promyelocytic, Acute; Liver Neoplasms; Transglutaminases; Tretinoin