scholarly journals Cytotoxic Activity and Antiproliferative Effects of Crude Skin Secretion from Physalaemus nattereri (Anura: Leptodactylidae) on in vitro Melanoma Cells

Toxins ◽  
2015 ◽  
Vol 7 (10) ◽  
pp. 3989-4005 ◽  
Author(s):  
Andréa Carvalho ◽  
César Márquez ◽  
Ricardo Azevedo ◽  
Graziella Joanitti ◽  
Osmindo Júnior ◽  
...  
2015 ◽  
Vol 9 (4) ◽  
pp. 172-177 ◽  
Author(s):  
Cínthia Caetano Bonatto ◽  
Graziella Anselmo Joanitti ◽  
Luciano Paulino Silva

Endocrinology ◽  
2015 ◽  
Vol 156 (5) ◽  
pp. 1630-1636 ◽  
Author(s):  
Tae-Kang Kim ◽  
Zongtao Lin ◽  
Wei Li ◽  
Russel J. Reiter ◽  
Andrzej T. Slominski

Previously, we demonstrated that skin cells metabolize melatonin to 6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine and 5-methoxytryptamine. In this study, we determined that N1-acetyl-5-methoxykynuramine (AMK) is endogenously produced in the human epidermis from melatonin through the kynuric pathway. The epidermal content of AMK (average from 13 subjects) is 0.99 ± 0.21 ng/mg protein, being significantly higher in African Americans (1.50 ± 0.36 ng/mg protein) than in Caucasians (0.56 ± 0.09 ng/mg protein). It is especially high in young African Americans. The levels do not differ significantly between males and females. In vitro testing using HaCaT keratinocytes has shown that exogenously added melatonin is metabolized to AMK in a dose dependent manner with a Vmax = 388 pg/million cells and Km = 185 μM. AMK production is higher in melanized than in amelanotic melanoma cells. Testing of DNA incorporation shows that AMK has antiproliferative effects in HaCaT and SKMEL-188 cells (nonpigmented and pigmented). AMK also inhibits growth of normal melanocytes but has no significant effect on melanogenesis or cell morphology. These findings indicate that antiproliferative effects of AMK are not related to melanin pigmentation. In summary, we show for the first time that AMK is produced endogenously in the human epidermis, that its production is affected by melanin skin pigmentation, and that AMK exhibits antiproliferative effects in cultured keratinocytes and melanoma cells.


Planta Medica ◽  
2017 ◽  
Vol 83 (16) ◽  
pp. 1289-1296 ◽  
Author(s):  
Geanne Conserva ◽  
Natalia Girola ◽  
Carlos Figueiredo ◽  
Ricardo Azevedo ◽  
Sasha Mousdell ◽  
...  

Abstract Guarea macrophylla is a Brazilian plant species that has been used in folk medicine to treat a range of diseases. Our ongoing work focuses on the discovery of new bioactive natural products derived from Brazilian flora. The current study describes the identification of cytotoxic compounds from the EtOH extract of leaves from G. macrophylla using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of four compounds: cycloart-23E-ene-3β,25-diol (1), (23S*,24S*)-dihydroxycicloart-25-en-3-one (2), isopimara-7,15-diene-2α,3β-diol (3), and isopimara-7,15-dien-3β-ol (4), in which 2 and 3 are identified as new derivatives. In vitro assays were conducted to evaluate the cytotoxic activity of compounds 1–4 against a panel of cancer cell lines and to determine the possible mechanism(s) related to the activity of the compounds on B16F10Nex2 cells. The most active compound 1 induced cytotoxic effects on tumor cells, with IC50 values of 18.3, 52.1, and 58.9 µM against HL-60, HeLa, and B16F10-Nex2 tumor cells, respectively. Furthermore, it was observed in melanoma cells that compound 1 induced several specific apoptotic hallmarks, such as morphological changes in the cell shape structure, nuclear DNA condensation, specific chromatin fragmentation, and disruption in the mitochondrial membrane potential, which are related to the intrinsic apoptotic pathway.


2012 ◽  
Vol 35 (3) ◽  
pp. 565-571 ◽  
Author(s):  
Paula R. O. Soares ◽  
Pollyana Laurindo de Oliveira ◽  
Cecília M. A. de Oliveira ◽  
Lucilia Kato ◽  
Lídia Andreu Guillo

1998 ◽  
Vol 79 (05) ◽  
pp. 1041-1047 ◽  
Author(s):  
Kathleen M. Donnelly ◽  
Michael E. Bromberg ◽  
Aaron Milstone ◽  
Jennifer Madison McNiff ◽  
Gordon Terwilliger ◽  
...  

SummaryWe evaluated the in vivo anti-metastatic activity of recombinant Ancylostoma caninum Anticoagulant Peptide (rAcAP), a potent (Ki = 265 pM) and specific active site inhibitor of human coagulation factor Xa originally isolated from bloodfeeding hookworms. Subcutaneous injection of SCID mice with rAcAP (0.01-0.2 mg/mouse) prior to tail vein injection of LOX human melanoma cells resulted in a dose dependent reduction in pulmonary metastases. In order to elucidate potential mechanisms of rAcAP’s anti-metastatic activity, experiments were carried out to identify specific interactions between factor Xa and LOX. Binding of biotinylated factor Xa to LOX monolayers was both specific and saturable (Kd = 15 nM). Competition experiments using antibodies to previously identified factor Xa binding proteins, including factor V/Va, effector cell protease receptor-1, and tissue factor pathway inhibitor failed to implicate any of these molecules as significant binding sites for Factor Xa. Functional prothrombinase activity was also supported by LOX, with a half maximal rate of thrombin generation detected at a factor Xa concentration of 2.4 nM. Additional competition experiments using an excess of either rAcAP or active site blocked factor Xa (EGR-Xa) revealed that most of the total factor Xa binding to LOX is mediated via interaction with the enzyme’s active site, predicting that the vast majority of cell-associated factor Xa does not participate directly in thrombin generation. In addition to establishing two distinct mechanisms of factor Xa binding to melanoma, these data raise the possibility that rAcAP’s antimetastatic effect in vivo might involve novel non-coagulant pathways, perhaps via inhibition of active-site mediated interactions between factor Xa and tumor cells.


2016 ◽  
Vol 16 (9) ◽  
pp. 1172-1183 ◽  
Author(s):  
Lamia Benguedouar ◽  
Mesbah Lahouel ◽  
Sophie C. Gangloff ◽  
Anne Durlach ◽  
Florent Grange ◽  
...  

Melanoma is the more dangerous skin cancer, and metastatic melanoma still carries poor prognosis. Despite recent therapeutic advances, prolonged survival remains rare and research is still required. Propolis extracts from many countries have attracted a great deal of attention for their biological properties. We here investigated the ability of an ethanolic extract of Algerian propolis (EEP) to control melanoma tumour growth when given to mice bearing B16F1melanoma tumour either as preventive or as therapeutic treatment. EEP given after tumour occurrence increased mice survival (+30%) and reduced tumour growth (-75%). This was associated with a decrease of the Mitotic Index (-75%) and of Ki-67 (-50%) expression. When given either before or both before and after tumour occurrence, EEP reduced tumour growth but without prolonging mice life. Isolation of B16F1 melanoma cells from resected tumour showed that preventive and curative EEP treatments reduced invasiveness by 55% and 40% respectively compared to control. Galangin, one of the most abundant flavonoids in propolis, significantly reduced the number of melanoma cells in vitro and induced autophagy/apoptosis dose dependently. In conclusion, we showed that EEP reduced melanoma tumour progression/dissemination and could extend mice lifespan when used as therapeutic treatment. Then, EEP may help patients with melanoma when used as a complementary therapy to classical treatment for which autophagy is not contraindicated.


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