RESUMEN
Pardaxin (H-GFFALIPKIISSPLFKTLLSAVGSALSSSGGQE-OH), a 33-amino-acid polypeptide, is an antimicrobial peptide (AMP) isolated from the marine fish species Pardachirus marmoratus. Pardaxin shows antibacterial and antitumor activities. However, pardaxin-induced inhibition of oral cancer and the mechanism of tumor reduction in buccal pouch carcinogenesis after pardaxin painting remain undetermined. Additionally, the toxic effects of pardaxin on normal tissue remain unclear. The present study investigated the anticancer activity of pardaxin in oral squamous cell carcinoma (OSCC) cells in the hamster buccal pouch model with or without 7,12-dimethylbenz[a]anthracene (DMBA) pretreatment. This is the first study to confirm the effects of pardaxin on normal tissue and its nontoxic effects in vivo. Cell viability assays and colony formation tests in OSCC cell lines (SCC-4) demonstrated that pardaxin reduced cell viability in a dose-dependent manner. Immunofluorescence staining of cleaved caspase-3 in SCC-4 cells revealed that expression of activated caspase-3 in SCC-4 cells significantly increased after 24-h treatment with pardaxin. Additionally, a cell cycle analysis indicated that pardaxin treatment resulted in the cell cycle arrest of SCC-4 cells in the G2/M phase, thereby limiting cell proliferation. Furthermore, pardaxin treatment substantially alleviated carcinogenesis in the DMBA-induced hamster buccal pouch model by lowering prostaglandin E2 levels. These results suggest that pardaxin is a potential marine drug for adjuvant chemotherapy for human OSCC and oral cancer.
Asunto(s)
Antineoplásicos/farmacología , Venenos de los Peces/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Línea Celular Tumoral/efectos de los fármacos , Cricetinae , Modelos Animales de Enfermedad , Venenos de los Peces/química , Venenos de los Peces/uso terapéutico , Humanos , Técnicas In Vitro , Ratones , Neoplasias de la Boca/tratamiento farmacológicoRESUMEN
Antimicrobial peptides (AMPs) have recently been determined to be potential candidates for treating drug-resistant bacterial infections. Pardaxin (GE33), a marine antimicrobial peptide, has been reported to possess antimicrobial function. In this study, we investigated whether pardaxin promoted healing of contaminated wounds in mice. One square centimeter of outer skin was excised from the ventral region of mice, and a lethal dose of methicillin-resistant Staphylococcus aureus (MRSA) was applied in the presence or absence of methicillin, vancomycin, or pardaxin. While untreated mice and mice treated with methicillin died within 3 days, mice treated with pardaxin survived infection. Pardaxin decreased MRSA bacterial counts in the wounded region and also enhanced wound closure. Reepithelialization and dermal maturation were also faster in mice treated with pardaxin than in mice treated with vancomycin. In addition, pardaxin treatment controlled excess recruitment of monocytes and macrophages and increased the expression of vascular endothelial growth factor (VEGF). In conclusion, these results suggest that pardaxin is capable of enhancing wound healing. Furthermore, this study provides an excellent platform for comparing the antimicrobial activities of peptide and nonpeptide antibiotics.
Asunto(s)
Antibacterianos/uso terapéutico , Venenos de los Peces/uso terapéutico , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Animales , Carga Bacteriana , Femenino , Ratones , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Infecciones Cutáneas Estafilocócicas/microbiología , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiologíaRESUMEN
We have previously reported that Lj-RGD3, a novel RGD-toxin protein, was isolated from the buccal gland of Lampetra japonica. The recombinant protein rLj-RGD3 has anti-invasive and anti-adhesive activity in tumor cells (HeLa cells) and endothelial cells (ECV304 cells) in vitro, and inhibits αvß3, αvß5, and ß1 integrin-mediated adhesion. In this study, we investigated the bioactivity of rLj-RGD3 in the drug-resistant MCF-7/Adr breast carcinoma cell line and drug-sensitive parental line MCF-7, and found that rLj-RGD3 inhibited the growth of both cell lines. Biological function studies revealed that rLj-RGD3 could induce the apoptosis in MCF-7/Adr, which was more prevalent than that in the drug-sensitive parental line MCF-7. In addition, rLj-RGD3 inhibited the adhesion of MCF-7/Adr cells to fibronectin. Furthermore, rLj-RGD3 prevented invasion of MCF-7/Adr cells through an artificial matrigel basement membrane. In summary, rLj-RGD3 may be used as a potential drug in multidrug-resistant breast cancer therapy.
Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Venenos de los Peces/uso terapéutico , Inmunotoxinas/uso terapéutico , Oligopéptidos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Femenino , Fibronectinas/metabolismo , Células HeLa , Humanos , Invasividad Neoplásica/prevención & controlRESUMEN
Quantitative determination of newly reported enzymes activity in the crude skin toxin (CST) of catfish revealed highest activities of hyaluronidase and lipase, lesser activities of phospholipase A2, lactate dehydrogenase (LDH), cholinesterase (CE), alkaline phosphatase (ALP), and aspartate transaminase (AST), and least activities of proteinase and 5-nucleotidase (5'-NT). The CST has a hemolytic activity of 54% and no ichthyotoxicity up to 500 ug/ml. The chosen dose of CST (LD12.5) showed a potential cytotoxic activity against solid Ehrlich carcinoma-bearing mice demonstrated by an increase in the mean survival time (238.8%) and tumor growth inhibition ratio (T/C) of 73%. The CST ameliorated the relative weights of heart and liver after three weeks, while modulating the elevation in the relative spleen weight throughout the treatment periods (three, six, and nine weeks). The levels of serum triglyceride, total cholesterol, and liver total lipids were normalized after three weeks, whereas the serum albumin and hepatic glycogen concentrations, as well as ALT, AST, 5'-NT, and G-6-Pase activities were ameliorated after 6 weeks. Serum levels of glucose, LDH, and creatine kinase (CK) activities were significantly modulated throughout the treatment periods. Histological examinations of the tumor and liver tissues of treated tumor-bearing animals were carried out. Tumor tissues showed many cytolytic and cytopathic changes after treatment, while liver tissues showed moderate dysplastic changes after six weeks of treatment, which became more marked after nine weeks.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Ehrlich/tratamiento farmacológico , Bagres , Venenos de los Peces/uso terapéutico , Piel/metabolismo , Animales , Antineoplásicos/toxicidad , Peso Corporal/efectos de los fármacos , Carcinoma de Ehrlich/enzimología , Carcinoma de Ehrlich/patología , Edema/inducido químicamente , Enzimas/sangre , Femenino , Venenos de los Peces/enzimología , Venenos de los Peces/toxicidad , Corazón/efectos de los fármacos , Océano Índico , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Ratones , Trasplante de Neoplasias , Tamaño de los Órganos/efectos de los fármacos , Bazo/efectos de los fármacosRESUMEN
The biology and toxicology of the lesser weeverfish, Trachinus vipera, is presented in a homeopathic repertory fashion to supplement the existing materia medica.