deoxycholic-acid and Melanoma

5-Fluorouracil (5-FU) is an antimetabolite drug widely used for the treatment of skin cancer. Despite its proven efficacy in treating malignancies, its systemic administration is limited due to severe side effects. To address this issue, topical delivery of 5-FU has been proposed as an alternative approach for the treatment of skin cancer, however, the poor permeability of 5-FU through the skin is still a challenge. Here, we introduced a pH-responsive micellar hydrogel system based on deoxycholic acid micelle (DCA Mic) and carboxymethyl chitosan hydrogel (CMC Hyd) to enhance 5-FU efficacy against skin cancer and reduce its systemic side effects by improving its delivery into the skin. The properties of the Mic/Hyd system were determined by Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta sizer, atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Drug release studies showed pH-dependent properties of the Hyd. The final formulation was demonstrated to have enhanced anticancer activity than 5-FU against the growth of melanoma cells. The 5-FU@Mic-Hyd could be a promising delivery platform with enhanced efficacy in the management of skin cancer without systemic toxicity.

Topics: Chitosan; Delayed-Action Preparations; Deoxycholic Acid; Drug Carriers; Drug Delivery Systems; Fluorouracil; Humans; Hydrogels; Melanoma; Micelles; Skin Neoplasms; Spectroscopy, Fourier Transform Infrared

Medications in dermatology are used in a variety of different methods and dosages and for numerous different diseases entities that are not approved by the US Food and Drug Administration (FDA); however, there are medications that have only recently hit the market that require our attention, as they are either FDA approved for the intended dermatologic use or could be effective in treating conditions that previously have been poorly managed.

Topics: Aminolevulinic Acid; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Arthritis, Psoriatic; Azetidines; Biphenyl Compounds; Carcinoma, Basal Cell; Cosmetic Techniques; Deoxycholic Acid; Dermatologic Agents; Drug Approval; Facial Dermatoses; Humans; Keratosis, Actinic; Melanoma; Oncolytic Virotherapy; Piperidines; Psoriasis; Pyridines; Scalp Dermatoses; Skin Neoplasms; United States; United States Food and Drug Administration

Orally absorbable anticancer medications have great advantages for conventional cancer therapies to patients. Here we evaluated the potent anticancer effect of orally absorbable LHD, a chemical conjugate of low-molecular-weight heparin and deoxycholic acid, on tumor graft growth models.. We characterized the angiogenic factors, such as VEGF, heparanase, and MMPs, of murine squamous cell carcinoma (SCC7), melanoma (B16F10) or lung carcinoma (LLC1). Two weeks after oral administration of LHD into these cancer-cell-bearing mice, we evaluated the antiangiogenic activity of LHD.. Although all cancer cells expressed the angiogenic factors, SCC7 cells had much higher angiogenic potential and grew rapidly after implantation into mice. When orally administered, LHD delayed tumor graft growth regardless of cancer types. Particularly, LHD powerfully diminished the SCC7-derived tumor growth. Also, the expression of angiogenic factors in all kinds of tumor tissues was decreased, thereby attenuating the neovascularization in tumor tissue.. Our study shows that LHD has potent anticancer and antiangiogenic effect on at least three kinds of tumor cells. LHD can be specifically used for preventing neovascularization in tumor tissue because it has therapeutical potential as an antiangiogenic drug and can be orally absorbed.

Topics: Absorption; Administration, Oral; Angiogenesis Inhibitors; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Deoxycholic Acid; Disease Models, Animal; Heparin, Low-Molecular-Weight; Humans; Immunohistochemistry; Lung Neoplasms; Melanoma; Mice; Mice, Inbred C57BL; Molecular Structure

(-)-Epigallocatechin gallate (EGCG), the main active polyphenol in green tea, is associated with antioxidant and anticancer activities.. The aim of this study was to evaluate the feasibility of using liposomes for intratumor distribution of EGCG and its derivative, (+)-catechin.. Liposomes containing egg phosphatidylcholine, cholesterol, or anionic surfactant in the presence of 15% ethanol were prepared. The physicochemical characteristics including vesicle size, zeta potential, drug entrapment, and drug release of liposomal formulations were determined. The liposomes containing EGCG were injected into basal cell carcinomas (BCCs), melanomas, and colon tumors to examine the tumor uptake of the drug. Liposomes were also incubated with a given number of BCC cells, and the cell viability was estimated.. Almost no drug molecules were observed when free EGCG was administered to BCCs. EGCG encapsulated in liposomes with deoxycholic acid (DA) and ethanol increased drug deposition by 20-fold as compared to the free form. The larger vesicle size of this formulation was suggested to be the predominant factor governing this enhancement. The liposomes without ethanol showed low or negligible enhancement on EGCG uptake in BCCs. Liposomes protected EGCG from degradation, resulting in the induction of greater BCC death compared to that by free EGCG at lower concentrations.. These results suggest that the intratumor injection of liposomes containing EGCG with moderate modification is an effective approach for increasing EGCG deposition in BCCs.

Topics: Animals; Antineoplastic Agents; Carcinoma, Basal Cell; Catechin; Cell Line, Tumor; Deoxycholic Acid; Drug Delivery Systems; Ethanol; Female; Humans; Liposomes; Melanoma; Mice; Mice, Inbred BALB C; Tea

Disc gel electrophoresis of tyrosinase solubilized by sodium deoxycholate (DOC) from the particle fraction of B16 mouse melanoma was carried out in the presence of DOC. A single tyrosinase band, considered to be T3, was detected at the Rx value of 0.60 against Coomassie brilliant blue. The T3 band which is located between T1 and T2 seems to be distinct from the soluble forms of tyrosinase. Its molecular weight was estimated to be 102,000. When treated with proteolytic enzymes or refrigerated, the T3 molecule converted into a molecule whose mobility was equivalent tothat of T1.

Topics: Animals; Catechol Oxidase; Deoxycholic Acid; Electrophoresis, Disc; Melanoma; Mice; Molecular Weight; Monophenol Monooxygenase; Neoplasms, Experimental; Solubility; Subcellular Fractions

Topics: Acid Phosphatase; Animals; Catechol Oxidase; Chick Embryo; Deoxycholic Acid; Dihydroxyphenylalanine; In Vitro Techniques; Melanins; Melanocytes; Melanoma; Microscopy, Electron, Scanning; Rats; Retinal Pigments; Swine; Trypsin; Vibration

Topics: Animals; Bile Acids and Salts; Cell Membrane; Deoxycholic Acid; Melanoma; Mice; Microscopy, Electron; Surface-Active Agents