astaxanthine and Liver-Neoplasms

Astaxanthin (AST) has attracted great interests in the scientific world because of its anti-oxidative, anti-inflammatory properties. And biodegradable materials, like chitosan, have been employed as the AST carrier to protect it from degradation and promote its bioavailability. However, the lack of pH responsiveness of these materials usually could not protect AST from the strong acidic gastric juices. In this study, calcium alginate (CA) microspheres, a pH responsive and biodegradable material, were prepared by a modified double emulsion technology and used as the AST encapsulation agent. Experimental results showed that the microparticles formed had a good degree of roundness, dispersity, encapsulation efficiency, and pH responsiveness. Cellular studies demonstrated that AST encapsulated in CA could inhibit hepatoma cells (HepG2 cell line) but it has relatively small or no impact on control hepatocytes (THLE-2 cell line). Furthermore, investigation of the underlying mechanism indicated that recovery of disorder of glucose metabolism by inhibiting aerobic glycolysis and promoting tricarboxylic acid cycle played an important part in the cell proliferation inhibition of hepatoma cells. As suggested above, AST could be a very promising therapeutic agent of liver cancer in clinical trials.

Topics: Alginates; Capsules; Carcinoma, Hepatocellular; Cell Line; Cell Proliferation; Chitosan; Drug Liberation; Hep G2 Cells; Humans; Liver Neoplasms; Microspheres; Particle Size; Reactive Oxygen Species; Xanthophylls

Hepatocellular carcinoma (HCC) is a malignant tumor that can cause systemic invasion; however, the exact etiology and molecular mechanism are unknown. Astaxanthin (ASX), a powerful antioxidant, has efficient anti-oxidant, anti-inflammatory, and other activities, and has great research prospects in cancer therapy. We selected the human hepatoma cell lines, LM3 and SMMC-7721, to study the anti-tumor effect and related mechanisms of ASX. The cell lines were treated with different concentrations of ASX, and its solvent DMSO as a control, for different time periods and the results were determined using CCK8, qRT-PCR, WB, apoptotic staining, and flow cytometry. ASX induced significant apoptosis of HCC cells, and its effect may have been caused by NF-κB p65 and Wnt/β-catenin down-regulation via negative activation of PI3K/Akt and ERK. Antitumor research on ASX has provided us with a potential therapy for patients with hepatomas.

Topics: Antineoplastic Agents; Apoptosis; beta Catenin; Carcinoma, Hepatocellular; Cell Line, Tumor; Dose-Response Relationship, Drug; Down-Regulation; Flow Cytometry; Humans; Liver Neoplasms; Transcription Factor RelA; Wnt Proteins; Xanthophylls

We designed to study the role of mitochondria in astaxanthin-induced apoptosis in hepatocellular carcinoma cells. Effect of astaxanthin on cell proliferation was studied by using methyl thiazolyl tetrazolium (MTT) in three tumor cell lines (CBRH-7919, SHZ-88 and Lewis) and normal human hepatocyte HL-7702 cell. Cell apoptosis rate, changes of mitochondrial morphology, mitochondrial transmembrane potential and electron transport chain were evaluated respectively. Expressions of B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were detected by Western blot. Results as following, astaxanthin had little effect on HL-7702 cell, however its inhibition was most pronounced in CBRH-7919 cell line with an IC₅₀ of 39 µM. This dose of astaxanthin and CBRH-7919 cell line were chosen for further studies. Astaxanthin could induce cell apoptosis and mitochondrial membrane damage. The mitochondrial transmembrane potential and function of electron transport chain were decreased. The expression of Bcl-2 protein was down-regulated but that of Bax protein was up-regulated. In conclusion, astaxanthin showed anticancer effect by inducing cell apoptosis through the regulation of mitochondrial-dependent manner.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Electron Transport Chain Complex Proteins; Hepatocytes; Humans; Inhibitory Concentration 50; Liver Neoplasms; Membrane Potential, Mitochondrial; Mitochondria, Liver; Rats; Signal Transduction; Up-Regulation; Xanthophylls

We investigated the effects of astaxanthin on the antitumor effector activity of natural killer (NK) cells suppressed by stress in mice in order to define the immunological significance of astaxanthin (ASX) when combined with restraint stress treatment. When the mice were treated with restraint stress alone, the total number of spleen cells, and the level NK cell activity per spleen were reduced to a nadir on day 3. The stress also caused a significant increase in the lipid peroxidation of liver tissue. ASX (100 mg/kg/day, p.o., 4 days) improved the immunological dysfunction induced by restraint stress. On the other hand, metastatic nodules were observed in the livers of syngenic DBA/2 mice on day 12 after inoculation of P815 mastocytoma cells. Hepatic metastasis was promoted further by restraint stress when applied on day 3 before the inoculation of P815. Daily oral administration of ASX (1 mg/kg/day, p.o., 14 days) markedly attenuated the promotion of hepatic metastasis induced by restraint stress. These results suggested that astaxanthin improves antitumor immune responses by inhibiting of lipid peroxidation induced by stress.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; beta Carotene; Cells, Cultured; Female; Immunosuppressive Agents; Killer Cells, Natural; Lipid Peroxidation; Liver; Liver Neoplasms; Mast-Cell Sarcoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasm Metastasis; Neoplasm Transplantation; Restraint, Physical; Stress, Psychological; Thiobarbituric Acid Reactive Substances; Tissue Distribution; Tumor Cells, Cultured; Xanthophylls