Melanin is one of the most widely distributed pigments and is found in bacteria, fungi, plants and animals. It is a heterogeneous polyphenol-like biopolymer with a complex structure and colors varying from yellow to black.1) The color of mammalian skin and hair is determined by a number of factors, the most important of which is the degree and distribution of melanin pigmentation. Melanin is secreted by melanocyte cells distributed in the basal layer of the dermis.2)The role of melanin is to protect the skin from ultraviolet (UV) damage by absorbing UV sunlight and removing reactive oxygen species (ROS). Melanin is formed through a series of oxidative reactions involving the amino acid tyrosine in the presence of tyrosinase. 3)Tyrosinase (monophenol monooxygenase EC 1.14.18.1) is a copper-containing enzyme widely found in plants and animals.4) It is known to be a key enzyme for melanin biosynthesis in plants, microorganisms and mammalian cells. The enzyme catalyzes two distinct reactions: the hydroxylation of monophenols to o-diphenols (monophenolase activity), and the oxidation of o-diphenols to o-quinones (diphenolase activity).5) Quinones are highly reactive compounds and can polymerize spontaneously to form high-molecular-weight compounds or brown pigment (melanin).6) These quinones can also react with amino acids and proteins that enhance the brown color produced. Because tyrosinase is one of the most important key enzymes in the insect molting process, investigation of its inhibitors may be important in finding alternative insect control agents.3) Many tyrosinase inhibitors have been tested in cosmetics and pharmaceuticals as a way of preventing overproduction of melanin in epidermal layers.7-9) Among the conventional skin-whitening agents, hydroquinone (HQ) is one of those most often prescribed.10,11) HQ can cause reversible inhibition of the cellular metabolism by affecting both DNA and RNA synthesis. Hence, it is considered to be a potent melanocyte cytotoxic agent but has also been reported to induce mutations. Arbutin, a naturally occurring HQ b-D-gluconopyranoside, which is depigmented at non-cytotoxic concentrations, acts similarly HQ. In both normal human melanocytes and melanoma cells, arbutin induces a decrease of tyrosinase activity without affecting messenger RNA (mRNA) expression.12) Kojic acid is an antibiotic produced by many species of Asperigillus and Penicillum. The depigmenting action is attributed to the chelating ability and a good scavenger of free radicals. 13,14) In our preliminary screening using mushroom tyrosinase, the extract of Gastrodia elata Blume (Orchidaceae) (GE) was found to show significant inhibitory activity for tyrosine hydroxylation. 4HBA was characterized as the principal inhibitor from GE extract. 4HBA is a phenolic compound and is synthesized from phenol and formaldehyde by hydroxymethylation. Early studies pointed out that it had sedative and anticonvulsive effects by acting on central GABA receptors, [15][16][17][18][19][20][21][22][23] and possessed antioxidant...

BackgroundLung cancer is one of the leading causes of cancer related deaths worldwide. Marine microalgae are a source of biologically active compounds and are widely consumed as a nutritional supplement in East Asian countries. It has been reported that Chlorella or Chlorella extracts have various beneficial pharmacological compounds that modulate immune responses; however, no studies have investigated the anti-cancer effects of Chlorella sorokiniana (CS) on non-small cell lung cancer (NSCLC).MethodsIn this study, we evaluated the anti-cancer effects of CS in two human NSCLC cell lines (A549 and CL1-5 human lung adenocarcinoma cells), and its effects on tumor growth in a subcutaneous xenograft tumor model. We also investigated the possible molecular mechanisms governing the pharmacological function of CS.ResultsOur results showed that exposure of the two cell lines to CS resulted in a concentration-dependent reduction in cell viability. In addition, the percentage of apoptotic cells increased in a dose-dependent manner, suggesting that CS might induce apoptosis in human NSCLC cells. Western blot analysis revealed that exposure to CS resulted in increased protein expression of the cleaved/activated forms of caspase-3, caspase-9, and PARP, except caspase-8. ZDEVD (caspase-3 inhibitor) and Z-LEHD (caspase-9 inhibitor) were sufficient at preventing apoptosis in both A549 and CL1-5 cells, proving that CS induced cell death via the mitochondria-mediated apoptotic pathway. Exposure of A549 and CL1-5 cells to CS for 24 h resulted in decreased expression of Bcl-2 protein and increased expression of Bax protein as well as decreased expression of two IAP family proteins, survivin and XIAP.ConclusionsWe demonstrated that CS induces mitochondrial-mediated apoptosis in NSCLC cells via downregulation of Bcl-2, XIAP and survivin. In addition, we also found that the tumors growth of subcutaneous xenograft in vivo was markedly inhibited after oral intake of CS.

Chlorella sorokiniana (CS) is a unicellular green alga. The extracts of Chlorella have been used as treatments for relieving hypertension and modulating immune response. The detailed mechanisms are not clear yet. In this study, we sought to study the molecular mechanisms for the polysaccharide fraction of CS-induced immune response. We pulsed dendritic cells (DCs) with CS and found that CS could maturate DCs. CS-maturated DC could activate naïve T cells and stimulate T-cell proliferation and IFN-γ secretion. Furthermore, CS activated PI3K and MAPKs signaling pathways in DCs by interacting with TLR4 receptor. These CS-activated signaling pathways could further activate NF-κB and induce IL-12 production in DCs. This study provides molecular mechanisms for CS-induced DCs activation and immune response.

Dendritic cells (DCs) play an important role in connecting innate and adaptive immunity. Thus, DCs have been regarded as a major target for the development of immunomodulators. In this study, we examined the effect of dextromethorphan (DXM), a common cough suppressant with a high safety profile, on the activation and function of DCs. In the presence of DXM, the LPS-induced expression of the costimulatory molecules in murine bone marrow-derived dendritic cells (BMDCs) was significantly suppressed. In addition, DXM treatment reduced the production of reactive oxygen species (ROS), proinflammatory cytokines, and chemokines in maturing BMDCs that were activated by LPS. Therefore, DXM abrogated the ability of LPS-stimulated DCs to induce Ag-specific T-cell activation, as determined by their decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. Moreover, the inhibition of LPS-induced MAPK activation and NF-κB translocation may contribute to the suppressive effect of DXM on BMDCs. Remarkably, DXM decreased the LPS-induced surface expression of CD80, CD83, and HLA-DR and the secretion of IL-6 and IL-12 in human monocyte-derived dendritic cells (MDDCs). These findings provide a new insight into the impact of DXM treatment on DCs and suggest that DXM has the potential to be used in treating DC-related acute and chronic diseases.

Cortex periplocae is the dried root bark of Periploca sepium Bge., a traditional Chinese herb medicine. It contains high amounts of cardiac glycosides. Several cardiac glycosides have been reported to inhibit tumor growth or induce tumor cell apoptosis. We extracted and purified cortex periplocae and identified periplocin as the active ingredient that inhibited the growth of TNF-related apoptosis-inducing ligand-(TRAIL-) resistant hepatocellular carcinoma cells. The antitumor activity of periplocin was further increased by TRAIL cotreatment. Periplocin sensitized TRAIL-resistant HCC through the following two mechanisms. First, periplocin induced the expression of DR4 and FADD. Second, the cotreatment of TRAIL and periplocin suppressed several inhibitors of apoptosis (IAPs). Both mechanisms resulted in the activation of caspase 3, 8, and 9 and led to cell apoptosis. In addition, intraperitoneal injection (IP) of periplocin repressed the growth of hepatocellular carcinoma (HCC) in xenograft tumor model in mice. In summary, periplocin sensitized TRAIL-resistant HCC cells to TRAIL treatment and resulted in tumor cell apoptosis and the repression of tumor growth in vivo.