Furanoditerpenes from Pterodon pubescens benth with selective in vitro anticancer activity for prostate cell line

Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6α-acetoxi 7β-hydroxy-vouacapan 1 and four known diterpene furans 2, 3, 4, 5. The compounds were evaluated for in vitro cytotoxic activities against human normal cells and tumour cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-H460 (lung, non-small cells), OVCAR-03 (ovarian), PC-3 (prostate), HT-29 (colon), 786-0 (renal), K562 (leukemia) and NCI-ADR/RES (ovarian expressing phenotype multiple drugs resistance). Results were expressed by three concentration dependent parameters GI50 (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC50 (concentration that produces -50% growth, a cytotoxicity parameter). Also, in vitro cytotoxicity was evaluated against 3T3 cell line (mouse embryonic fibroblasts). Antiproliferative properties of compounds 1, 4 and 5 are herein reported for the first time. These compounds showed selectivity in a concentration-dependent way against human PC-3. Compound 1 demonstrated selectivity 26 fold more potent than the positive control, doxorubicin, for PC-3 (prostrate) cell line based on GI50 values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC50 value) with positive control (doxorubicin) suggested that compound 1 was less toxic

Furanoditerpenes from Pterodon pubescens benth with selective in vitro anticancer activity for prostate cell line

Activity guided fractionation of Pterodon pubescens Benth. methylene chloride-soluble fraction afforded novel 6α-acetoxi 7β-hydroxy-vouacapan 1 and four known diterpene furans 2, 3, 4, 5. The compounds were evaluated for in vitro cytotoxic activities against human normal cells and tumour cell lines UACC-62 (melanoma), MCF-7 (breast), NCI-H460 (lung, non-small cells), OVCAR-03 (ovarian), PC-3 (prostate), HT-29 (colon), 786-0 (renal), K562 (leukemia) and NCI-ADR/RES (ovarian expressing phenotype multiple drugs resistance). Results were expressed by three concentration dependent parameters GI50 (concentration that produces 50% growth inhibition), TGI (concentration that produces total growth inhibition or cytostatic effect) and LC50 (concentration that produces -50% growth, a cytotoxicity parameter). Also, in vitro cytotoxicity was evaluated against 3T3 cell line (mouse embryonic fibroblasts). Antiproliferative properties of compounds 1, 4 and 5 are herein reported for the first time. These compounds showed selectivity in a concentration-dependent way against human PC-3. Compound 1 demonstrated selectivity 26 fold more potent than the positive control, doxorubicin, for PC-3 (prostrate) cell line based on GI50 values, causing cytostatic effect (TGI value) at a concentration fifteen times less than positive control. Moreover comparison of 50% lethal concentration (LC50 value) with positive control (doxorubicin) suggested that compound 1 was less toxic.O fracionamento biomonitorado do extrato diclorometânico das sementes de Pterodon pubescens Benth forneceu o 6α-acetóxi-7β-hidróxi-vouacapano 1 (inédito), além de quatro diterpenos furânicos (2, 3, 4 e 5). A atividade antiproliferativa dos compostos foi avaliada in vitro contra as linhagens de células tumorais humanas UACC-62 (melanoma), MCF-7 (mama), NCI-H460 (pulmão), OVCAR-03 (ovário), PC-3 (próstata), HT-29 (colon), 786-0 (rim), K562 (leucemia) e NCI-ADR/RES (ovário com fenótipo de resistência a múltiplos fármacos). Os resultados foram expressos em três concentrações efetivas GI50 (concentração para que ocorra 50% de inibição de crescimento), TGI (concentração que resulta em inibição total de crescimento) e LC50 (concentração que resulta em 50% de morte celular). A citotoxicidade in vitro foi avaliada também frente a uma linhagem de célula murina normal (3T3). Este é o primeiro relato de atividade anticâncer para os compostos 1, 4 e 5, que apresentaram grande seletividade, dependente da concentração, para PC-3. O composto 1 foi 26 vezes mais potente para inibir 50% do crescimento (GI50) de PC-3, 15 vezes mais citostático (TGI) e 6 vezes menos tóxico (LC50) quando comparado com Doxorrubicina (controle).569575Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Antiulcerative and antinociceptive activities of casein and whey proteins

The aim of this study was to evaluate the antiulcerative and antinociceptive activities of milk proteins using the induced gastric ulcer with ethanol rat model and the acetic acid-induced writhing mouse model. Casein (CN), (100, 300, and 1000 mg kg) doses presented antiulcerative activity on a dose-dependent manner with values of 30.8%, 41.4%, and 57.0% of inhibition measured using the ulcerative lesions index (ULI), respectively. Whey protein concentrate (WPC), (100, 300, and 1000 mg kg) doses presented antiulcerative activity on a dose-dependent manner with values of 48.9%, 65.5%, and 68.22% of ULI inhibition, respectively. CN, casein hydrolysates (CNH), WPC, and whey protein hydrolysates (WPH), (3, 10, and 30 mg kg) doses presented antinociceptive activity using the acetic acid-induced writhing in the mouse model. CN (30 mg kg) presented a value of 40% of inhibition writhing, and CNH (30 mg kg) presented antinociceptive activity with a value up to 46% of writhing inhibition. WPC (30 mg kg) presented a value of 52.50%, and WPH (30 mg kg) presented antinociceptive activity with a value up to 88.00% of writhing inhibition. In conclusion, CN and WPC demonstrated in vivo antiulcerative properties and represent a promising alternative to be used as protectors of the gastric mucosa. CNH and WPH demonstrated in vivo antiulcerative properties and represent a promising alternative to be used as natural analgesic.This work has received financial support from the projects CYTED110AC0386 (IBEROFUN), AGL2011-24643, FEDER-INNTERCONECTA-GALICIA (ENVELLEFUN), FP7-SME-2012-315349 (FOFIND), and CNPq (Brazil).Peer Reviewe

Pharmacological characterization of Solanum cernuum Vell.: 31-norcycloartanones with analgesic and anti-inflammatory properties

Cycloeucalenone (1) and 24-oxo-31-norcycloartanone (2) obtained from Solanum cernuum Vell. were assayed to explore their pharmacologic roles. Previous studies showed that (2) has selective activity against lung tumor cell line (NCIH460) which expresses high levels of COX-2, suggesting its role in inflammatory process, and also a link between chronic inflammation and cancer-associated process. Dichloromethane crude extract (DCE) significantly reduced writhing and stretching induced by 0.8 % acetic acid at a dose of 100, 300, and 600 mg/kg, po; oral administration of different doses of (1) and (2) also displayed significant analgesic and anti-inflammatory effects in the writhing acetic acid test (p < 0.0001). Selected oral doses of both compounds (100 and 50 mg/kg) were assayed in the carrageenan-induced paw edema model. Compound (2) showed significant activity during the early phase (1.5–6 h) and also in the late phase (48 h) (p < 0.01). The anti-nociceptive activity observed for the compounds (1) and (2) and DCE was found to be related to the inhibition of different mediators involved in inflammation and nociceptive process. Both compounds decreas COX-2 protein expression, although only compound (2) reached a significant response (p < 0.05 vs control). However, in vitro Sirtuin 1 activity and TNF-a production in THP-1 macrophages were not affected