curcumin and Hepatoblastoma

We developed Cur nanosuspension (Cur-NS) with PVPK30 and SDS as stabilizers to improve poor water solubility and short biological half-time of Cur.. Physicochemical characterization of Cur-NS was characterized systematically. The in-vitro dissolution, cytotoxicity and in-vivo pharmacokinetic experiments of Cur-NS were also evaluated.. Scanning electron microscope indicated that the morphologies of Cur-NS were spherical or ellipsoidal in shape. X-ray diffraction verified that Cur was successfully developed as nanoparticles with an amorphous phase in Cur-NS. Fourier transform infrared spectroscopy suggested there was no degradation about Cur in the Cur-NS. Furthermore, the in-vitro study showed that the cumulative release of the Cur-NS was 82.16 ± 2.62% within 34 h and the cytotoxicity of the Cur-NS against HepG2 cells was much better than raw Cur. Besides, in-vivo pharmacokinetics in rats by intravenous injection displayed that the in-vivo process of Cur-NS pertained to two-compartment model. Meanwhile, the t1/2 and AUC0-t of Cur-NS were enhanced by 11.0-fold and 4.2-fold comparing to Cur solution.. The Cur-NS significantly increased the water solubility and half-time of Cur, suggesting its potential as a nanocarrier in the delivery of Cur for future clinical application.

Topics: Animals; Antineoplastic Agents, Phytogenic; Area Under Curve; Biological Availability; Curcuma; Curcumin; Drug Delivery Systems; Female; Hep G2 Cells; Hepatoblastoma; Humans; Liver Neoplasms; Male; Nanoparticles; Particle Size; Pharmaceutical Solutions; Polyvinyls; Rats, Sprague-Dawley; Sodium Dodecyl Sulfate; Solubility; Spectroscopy, Fourier Transform Infrared; Water; X-Ray Diffraction

Hypoxia-inducible factor-1 (HIF-1) has a central role in cellular responses to hypoxia, including the transcriptional activation of a number of genes involved in angiogenesis in tumors. We found that curcumin, a natural, biologically active compound isolated from the commonly used spice turmeric, significantly decreases hypoxia-induced HIF-1alpha protein levels in HepG2 hepatocellular carcinoma cells. Moreover, curcumin suppressed the transcriptional activity of HIF-1 under hypoxia, leading to a decrease in the expression of vascular endothelial growth factor (VEGF), a major HIF-1 target angiogenic factor. Curcumin also blocked hypoxia-stimulated angiogenesis in vitro and down-regulated HIF-1alpha and VEGF expression in vascular endothelial cells. These findings suggest that curcumin may play pivotal roles in tumor suppression via the inhibition of HIF-1alpha-mediated angiogenesis.

Topics: Cell Growth Processes; Cell Hypoxia; Curcumin; Down-Regulation; Endothelial Cells; Hepatoblastoma; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Neovascularization, Pathologic; RNA, Messenger; Transcriptional Activation; Transfection; Vascular Endothelial Growth Factor A

Apoptosis of HepG2 cells triggered by various agents is characterized in an attempt to delineate the common apoptosis signaling pathway in human hepatoma cells. Several hallmarks of apoptosis, including DNA laddering, chromatin condensation and fragmentation, and an apoptosis specific cleavage of 28S and 18S ribosomal RNA were observed after treatment with curcumin. Curcumin treatment however did not alter the expression levels of Bcl-2 and Bax proteins. p53 protein accumulated slowly and decreased abruptly after reaching the maximum. Conversely, c-Myc protein decreased initially and subsequently increased preceding the onset of apoptosis. The accumulation of p53 protein is not due to increased levels of p53 mRNA and does not result in growth arrest. Staurosporine, quinacrine, ultraviolet irradiation, hydrogen peroxide, and cyclohexamide are all capable of triggering apoptosis in HepG2 cells. While most of these agents affect the expression levels of p53 and c-Myc similarly, none of them altered the expression levels of the Bcl-2 and Bax proteins. In conclusion, these data suggest that p53 and c-Myc may play a more important role in the apoptosis signaling pathway in HepG2 cells, than the bcl-2 gene family.

Topics: Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Cell Cycle; Curcumin; Gene Expression Regulation, Neoplastic; Hepatoblastoma; Humans; Liver Neoplasms; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Proto-Oncogene Proteins c-myc; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured; Tumor Suppressor Protein p53