melanoma

Nicotinamide, a vitamin B3 derivative, is an inhibitor of SIRT1 (IC50=50-180 μM) and SIRT2 (IC50=2 μM). Nicotinamide can be used as a precursor of nicotinamide adenine dinucleotide or NAD+, which can be supplemented by dietary intake and can prevent or treat melanoglossia and pellagra.

Methyl 4-hydroxycinnamate is an esterified derivative of p-coumaric acid isolated from the flowers of Trixis michuacana var. longifolia, exhibiting antibacterial and anti-melanogenesis properties.

Picrocrocin is a natural product

Reticulol is an isocoumarin derivative produced by certain species of Streptomyces. Reticulol inhibits cAMP phosphodiesterase (IC50 = 41 µM). Recticulol (M.W. 222.2) exhibits a potent in vitro cytotoxicity against the human lung tumor cell line A427 and the mouse melanoma cell line B16F10.

Phloretin (NSC-407292) is a well-known inhibitor of eukaryotic urea transporters, blocks VacA-mediated urea and ion transport. Phloretin is a dihydrochalcone, a type of natural phenols. It can be found in apple tree leaves and the Manchurian apricot. It promotes potent antioxidative activities in peroxynitrite scavenging and the inhibition of lipid peroxidation. It has been found to inhibit the growth of several cancer cells and induce apoptosis of B16 melanoma and HL60 human leukemia cells.

1. Berberine (Umbellatine) is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism. 2. Berberine may as a broad-spectrum anti-microbial medicine, a complementary therapeutic agent for HIV/AIDS. 3. Berberine seems to act as an herbal antidepressant and a neuroprotector against neurodegenerative disorders. 4. Berberine is used in histology for staining heparin in mast cells. As a natural dye, berberine has a colour index of 7516. 5. Berberine reduces hepatic fat content in rats with nonalcoholic fatty liver disease; also prevents proliferation of hepatic stellate cells (HSCs), which are central for the development of fibrosis during liver injury. 6. Berberine can ameliorate proinflammatory cytokines-induced intestinal epithelial tight junction damage in vitro, and berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states. 7. Berberine has antineoplastic effects, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma, etc.

1. Cinnamaldehyde (Cinnamic Aldehyde) has antipyretic activity. 2. Cinnamaldehyde is a sedative agent. 3. Cinnamaldehyde inhibits invasive capabilities of MDA-MB-435S cells was correlated with down-regulating the expression of miR-27a. 4. Cinnamaldehyde induces the generation of reactive oxygen species and exerts vasodilator and anticancer effects. 5. Cinnamaldehyde appears to be a promising candidate as an adjuvant in combination therapy with 5-fluorouracil (5-FU) and oxaliplatin (OXA), two chemotherapeutic agents used in CRC treatment. The possible mechanisms of its action may involve the regulation of drugmetabolizing genes. 6. Cinnamaldehyde plays a certain role in inhibiting the occurrence and progression of melanoma and its action mechanism may be manifested by inhibiting expression of VEGF and HIF-α, thus blood vessel simulation and formation of new blood vessels of melanoma cells, and growth of tumors accordingly.

Cinnamic acid (β-Phenylacrylic acid) has potential use in cancer intervention,The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells.

1. 2,5-Dihydroxyacetophenone (Quinacetophenone) possess anti-anxiety, and neuroprotective qualities. 2. 2,5-Dihydroxyacetophenone (Quinacetophenone) reatment can induce a sustained activation of JNK, ERK1 2, and p38 MAPKs, it also can potentiate the pro-apoptotic and anti-proliferative effects of bortezomib in U266 cells. 3. 2,5-Dihydroxyacetophenone (Quinacetophenone) has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions. 4. 2,5-Dihydroxyacetophenone (Quinacetophenone) is an uncompetitive inhibitor of murine tyrosinase (K(I) 0.28mm), it strongly inhibits both melanogenesis and cellular tyrosinase activity in vitro in 3-isobutyl-1-methylxanthin-stimulated B16 mouse melanoma cells or in vivo in zebrafish and mouse models.

Methyl pentadecanoate is a natural product.

1. Chelidonine (Stylophorin) isolated from Chelidonium majus efficiently induced apoptosis in HeLa cells through possible alteration of p38-p53 and AKT PI3 kinase signalling pathways. 2. Chelidonine is a promising model compound for overcoming MDR and for enhancing cytotoxicity of chemotherapeutics, especially against leukaemia cells, its efficacy needs to be confirmed in animal models. 3. Chelidonine may be a potential therapeutic agent against metastasis of invasive human cancer cells, exhibits antimigratory and antiinvasive effects in MDA-MB-231 cells, by suppressing COL-induced integrin signaling, through inhibiting the formation of the IPP complex and subsequent downregulation of IPP downstream signaling molecules, such as Akt and ERK1 2.

Chamazulene (Dimethulene) is a terpenoid obtained from Matricaria chamomilla L.. It possesses anti-inflammatory and antioxidant activity, inhibits leukotriene B4 formation and can be used in the study of melanoma.

Barbigerone is a tumor angiogenesis, growth, and metastasis inhibitor in melanoma.

Citropten, a coumarin isolated from bergamot oil, has antiproliferative effects on human melanoma cell line A2058.

Hederacolchiside A1 (Raddeanoside R13) shows anti-leishmanial activity, it exhibits a strong antiproliferative activity on all stages of development of the parasite by altering membrane integrity and potential. Hederacolchiside A1 shows antiproliferation activities in three cancer cell lines with the IC50 value of 2.4 uM, it exhibits a preferential cytotoxicity on a pigmented melanoma cell line. It suppresses proliferation of tumor cells by inducing apoptosis through modulating PI3K Akt mTOR signaling pathway.

Noroxyhydrastinine exhibits potent melanogenesis-inhibitory activities, it inhibits melanogenesis, at least in part, by inhibiting the expression of protein levels of tyrosinase, TRP-1, and TRP-2 in α-MSH-stimulated B16 melanoma cells.

Ingenol disoxate, also known as LEO43204, is a Novel 4-Isoxazolecarboxylate Ester of Ingenol with Improved Properties for Treatment of Actinic Keratosis and Other Non-Melanoma Skin Cancers. Ingenol is a natural product found in the sap of the plant Euphor

Cytochalasin D is an actin inhibitor, the removal of actin stress fibers is crucial for the chondrogenic differentiation. It may be an inhibitor of some fertilization processes such as sperm penetration or sperm head decondensation. Cytochalasin D inhibit

Ajoene is a disulfide that has been found inA. sativumand has diverse biological activities, including antibacterial, anticancer, antiplatelet, and antioxidant properties.1,2,3,4It is active against Gram-positive (MICs = 5-160 µg/ml) and Gram-negative bacteria (MICs = 136-200 µg/ml), as well as yeasts (MICs = 10-20 µg/ml).1Ajoene is cytotoxic to mouse melanoma cells (IC50= 18 µM), as well as human colon, lung, mammary, and pancreatic cancer cells (IC50s = 7-41 µM).2It reduces tumor growth in a B16/BL6 mouse model of melanoma when administered at a dose of 25 mg/kg every other day and decreases the number of lung metastases when administered prior to tumor cell inoculation at doses ranging from 1-25 mg/kg. It inhibits ADP- or collagen-induced platelet aggregation in isolated baboon platelets when used at concentrations ranging from 75 to 150 µg/ml and in platelet-rich plasma isolated from baboons when administered at a dose of 25 mg/kg.3Ajoene (25 mg/kg) prevents thrombus formation on damaged arterial walls in heparinized pigs in anin situmodel of thrombogenesis.5It also reduces high-fat diet-induced hepatic steatosis, histopathological markers of liver damage, thiobarbituric acid reactive substances (TBARS) formation, and protein oxidation in a mouse model of non-alcoholic fatty liver disease (NAFLD).4 1.Naganawa, R., Iwata, N., Ishikawa, K., et al.Inhibition of microbial growth by ajoene, a sulfur-containing compound derived from garlicAppl. Environ. Microbiol.62(11)4238-4242(1996) 2.Taylor, P., Noriega, R., Farah, C., et al.Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 miceCancer Lett.239(2)298-304(2006) 3.Teranishi, K., Apitz-Castro, R., Robson, S.C., et al.Inhibition of baboon platelet aggregation in vitro and in vivo by the garlic derivative, ajoeneXenotransplantation10(4)374-379(2003) 4.Han, C.Y., Ki, S.H., Kim, Y.W., et al.Ajoene, a stable garlic by-product, inhibits high fat diet-induced hepatic steatosis and oxidative injury through LKB1-dependent AMPK activationAntioxid. Redox Signal.14(2)187-202(2011) 5.Apitz-Castro, R., Badimon, J.J., and Badimon, L.A garlic derivative, ajoene, inhibits platelet deposition on severely damaged vessel wall in an in vivo porcine experimental modelThromb. Res.75(3)243-249(1994)

Cytostatin is a natural antitumor inhibitor of cell adhesion to extracellular matrix, blocking adhesion of B16 melanoma cells to laminin and collagen type IV in vitro (IC50s = 1.3 and 1.4 μg/ml, respectively) and B16 cells metastatic activity in mice. It induces apoptosis of FS3 mouse fibrosarcoma cells (IC50 = 3.1 μg/ml). Cytostatin potently and selectively inhibits protein phosphatase 2A (PP2A; IC50 = 29 nM against the catalytic subunit), while having no effect against PP1, PP2B, or PP5.

Saikosaponin B2 acts on HCV E2 and inhibits infection by several genotypic strains and prevents binding of serum-derived HCV onto hepatoma cells. Saikosaponin B2 (5 μM) induces differentiation of B16 melanoma cells, with potentiation of expressions of tyr

1. Xanthatin has cytotoxic activity. 2. Xanthatin has antibacterial and antifungal activies against MRSA. 3. Xanthatin may have therapeutic potential against NSCLC. 4. Xanthatin can inhibit murine melanoma B16-F1 cell proliferation possibly associated wit

1. N-trans-Feruloyltyramine (Feruloyltyramine)(NTF) has hepatoprotective effect. 2. NTF has antioxidative activity against Aβ(1-42)-induced neuronal death. 3. NTF is likely to inhibit COX enzymes, thereby suppressing P-selectin expression on platelets, is a platelet aggregation inhibitor. 4. NTF inhibits melanogenesis in a dose-dependent manner, NTF induces downregulation of tyrosinase resulted in suppression of melanin biosynthesis in murine B16 melanoma cells.

Heptelidic acid (Koningic acid) is a sesquiterpenoid lactone antibiotic derived from the probiotic fungus Aspergillus oryzae, a selective GAPDH inhibitor. It downregulates caspase to inhibit etoposide-induced apoptosis. Heptelidic acid inhibits tau fibrillation in a concentration-dependent manner and exerts antitumor effects on extra-intestinal melanoma by controlling glyceraldehyde-3-phosphate dehydrogenase activity.