RESUMO
Several polyphenolic compounds were tested for the inhibition of lung metastasis induced by B16F10 melanoma cells in mice. Oral administration of polyphenols such as curcumin and catechin at concentrations of 200 nmol/kg body weight were found to inhibit the lung metastasis maximally as seen by the reduction in the number of lung tumor nodules (80%). Other polyphenols which inhibited the lung tumor nodule formation were rutin (71.2%), epicatechin (61%), naringin (27.2%) and naringenin (26.1%). The polyphenols which did not inhibit lung tumor nodule formation were quercetin, morin and ellagic acid. Consequent to the inhibition of the lung tumor nodules, the life span of animals treated with polyphenols was also found to be increased. Curcumin (143.85%), catechin (80.81%) and rutin (63.59%) had maximal increase in life span. The results indicate a possible use of these compounds in arresting the metastatic growth of tumor cells.
Assuntos
Catequina/farmacologia , Curcumina/farmacologia , Flavonoides , Melanoma Experimental/patologia , Metástase Neoplásica/prevenção & controle , Fenóis/farmacologia , Polímeros/farmacologia , Rutina/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Feminino , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Endogâmicos C57BL , Análise de SobrevidaRESUMO
The inhibitory effects of curcumin and catechin on lung metastasis induced by B16F-10 melanoma cells were studied in female C57BL/6 mice. Curcumin and catechin significantly (P < 0.001) inhibited lung tumour formation (89.3% and 82.2%, respectively) and significantly increased the life span (143.9% and 80.8%, respectively). Moreover, lung collagen hydroxyproline and serum sialic acid levels were found to be significantly (P < 0.001) lower in treated animals compared to the untreated controls. Curcumin and catechin treatment (10 microg/ml) significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix of the Boyden chamber. Gelatin zymographic analysis of the trypsin-activated B16F-10 melanoma cells sonicate revealed that curcumin- and catechin-treated zymograms did not show any metalloproteinase activity. Curcumin and catechin treatment did not inhibit the motility of B16F-10 melanoma cells across a polycarbonate filter in vitro. These findings suggest that curcumin and catechin inhibit the invasion of B16F-10 melanoma cells by inhibition of metalloproteinases, thereby inhibiting lung metastasis.
Assuntos
Antineoplásicos/farmacologia , Catequina/farmacologia , Curcumina/farmacologia , Neoplasias Pulmonares/prevenção & controle , Melanoma Experimental/secundário , Metástase Neoplásica/prevenção & controle , Animais , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Colágeno/química , Colágeno/metabolismo , Feminino , Gelatina/metabolismo , Hidroxiprolina/análise , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Melanoma Experimental/mortalidade , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Ácido N-Acetilneuramínico/sangue , Invasividade Neoplásica , Transplante de Neoplasias , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Five rasayanas and one of the ingredients Emblica officinalis (EO), were studied for their antimetastatic activity using B16F-10 melanoma cells in C57BL/6 mice. Simultaneous oral administration (50 mg/animal/dose) of Brahma Rasayana (BR) and Aswagandha Rasayana (AR) significantly reduced the lung tumour nodule formation by 71.28% (P < 0.001) and 55.6% (P < 0.001), respectively. Similarly, the lung collagen hydroxyproline content and the serum sialic acid levels were also low in BR treated (4.8 +/- 0.97 ug/m protein; 35.6 +/- 2.6 ug/ml serum) and AR treated animals (6.15 +/- 0.5 ug/mg protein; 56.3 +/- 8.7 ug/ml serum) compared to the untreated controls (10.43 +/- 0.7 ug/mg protein; 161.3 +/- 9.5 ug/ml serum). Narasimha Rasayana (NR), Amrithaprasam (AP), Chyavanaprasam (CP) and Emblica extract (EO) administration had no significant effect in the reduction of lung nodule formation and lung hydroxyproline and serum sialic acid contents which was similar to that of untreated controls. Life span of BR, AR and NR treated animals was found to be significantly increased. These results indicate that BR and AR possess antimetastatic activity against melanoma cells.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Melanoma Experimental/prevenção & controle , Extratos Vegetais/uso terapêutico , Animais , Neoplasias Pulmonares/patologia , Masculino , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Taxa de SobrevidaRESUMO
Caffeine, a methyl xanthine derivative, was studied to assess the effect on B16F10 melanoma induced experimental metastasis. Caffeine was administered at a dose of 100 and 50 mg/kg body weight by both routes, to tumour bearing animals. Solid tumour reduction studies with Caffeine showed a significant reduction in tumour volume for 100 mg/kg dose by both oral and i.p. routes. The Caffeine treated metastatic tumour bearing animals significantly (p<0.001) inhibited lung tumour nodules. Serum sialic acid levels and lung hydroxyproline contents in the treated groups were significantly (p<0.001) low, when compared with the untreated control animals. In the present study, our results suggest that Caffeine inhibits solid tumour development and pulmonary experimental metastasis induced by B16F10 melanoma cells, in murine model.
Assuntos
Cafeína/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Animais , Feminino , Hidroxiprolina/metabolismo , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/secundário , Masculino , Melanoma Experimental/sangue , Melanoma Experimental/secundário , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Ácido N-Acetilneuramínico/sangue , Transplante de Neoplasias , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/patologiaRESUMO
Aplidin (plitidepsin) is a novel marine-derived antitumor agent presently undergoing phase II clinical trials in hematological malignancies and solid tumors. Lack of bone marrow toxicity has encouraged further development of this drug for treatment of leukemia and lymphoma. Multiple signaling pathways have been shown to be involved in Aplidin-induced apoptosis and cell cycle arrest in G1 and G2 phase. However, the exact mechanism(s) of Aplidin action remains to be elucidated. Here we demonstrate that mitochondria-associated or -localized processes are the potential cellular targets of Aplidin. Whole genome gene-expression profiling (GEP) revealed that fatty acid metabolism, sterol biosynthesis and energy metabolism, including the tricarboxylic acid cycle and ATP synthesis are affected by Aplidin treatment. Moreover, mutant MOLT-4, human leukemia cells lacking functional mitochondria, were found to be resistant to Aplidin. Cytosine arabinoside (araC), which also generates oxidative stress but does not affect the ATP pool, showed synergism with Aplidin in our leukemia and lymphoma models in vitro and in vivo. These studies provide new insights into the mechanism of action of Aplidin. The efficacy of the combination of Aplidin and araC is currently being evaluated in clinical phase I/II program for the treatment of patients with relapsed leukemia and high-grade lymphoma.
Assuntos
Antineoplásicos/farmacologia , Citarabina/farmacologia , Depsipeptídeos/farmacologia , Mitocôndrias/efeitos dos fármacos , Trifosfato de Adenosina/biossíntese , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/transplante , Citarabina/administração & dosagem , Depsipeptídeos/administração & dosagem , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Células K562/efeitos dos fármacos , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Metilprednisolona/farmacologia , Camundongos , Camundongos SCID , Mitocôndrias/fisiologia , Mitoxantrona/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Peptídeos Cíclicos , Organismos Livres de Patógenos Específicos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Methylcholanthrene-induced sarcoma formation in mice was found to be effectively inhibited by the intraperitoneal injection of mistletoe extract (Iscador M). Induction of sarcoma and sarcoma-induced death were inhibited completely at a concentration of 1 mg Iscador/dose. The concentration needed for 50% inhibition was found to be 0.0166 mg Iscador/dose. Mistletoe extract was also found to inhibit lung metastasis induced by B16F10 melanoma cells in mice. Simultaneous administration of the Viscum album extract inhibited lung nodule formation by 92.0% and produced a 71.3% increase in life span.
Assuntos
Anticarcinógenos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Erva-de-Passarinho , Metástase Neoplásica/prevenção & controle , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas de Plantas , Plantas Medicinais , Animais , Feminino , Neoplasias Pulmonares/prevenção & controle , Neoplasias Pulmonares/secundário , Melanoma/patologia , Melanoma/prevenção & controle , Camundongos , Camundongos Endogâmicos C57BL , Sarcoma Experimental/tratamento farmacológico , Sarcoma Experimental/patologiaRESUMO
Iscador, an extract from the semi-parasitic plant Viscum album, was found to inhibit 20-methylcholanthrene-induced carcinogenesis in mice. Intraperitoneal administration of Iscador (1 mg/dose) twice weekly for 15 weeks could completely inhibit 20-methylcholanthrene-induced sarcoma in mice and protect these animals from tumour-induced death. Iscador was found to be effective even at lowered doses. After administration of 0.166, 0.0166 and 0.00166 mg/dose 67, 50 and 17% of animals respectively did not develop sarcoma.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Proteínas de Plantas , Sarcoma Experimental/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Feminino , Metilcolantreno/toxicidade , Camundongos , Sarcoma Experimental/induzido quimicamenteRESUMO
Two dietary soybean isoflavones, genistein and daidzein, were studied for the inhibition of lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. The isoflavone genistein at 200 mumol/kg body wt significantly inhibited (53.6%, p < 0.001) lung tumor nodule formation. The lung collagen hydroxyproline content and the serum sialic acid level, a marker of metastasis, were also significantly lower in these animals than in untreated tumor-bearing animals. Genistein treatment also increased the life span of the tumor-bearing animals (47.7%, p < 0.001). The isoflavone daidzein had no significant effect on the reduction of lung metastasis induced by B16F-10 melanoma cells.