scholarly journals Development of a Novel Experimental In Vitro Model of Isothiocyanate-induced Apoptosis in Human Malignant Melanoma Cells

2016 ◽  
Vol 36 (12) ◽  
pp. 6303-6310 ◽  
Author(s):  
THEODORA MANTSO ◽  
ARISTEIDIS P SFAKIANOS ◽  
AITHNE ATKINSON ◽  
IOANNIS ANESTOPOULOS ◽  
MELINA MITSIOGIANNI ◽  
...  
2019 ◽  
Vol 38 (3) ◽  
pp. 621-633
Author(s):  
Sotiris Kyriakou ◽  
Melina Mitsiogianni ◽  
Theodora Mantso ◽  
William Cheung ◽  
Stephen Todryk ◽  
...  

Author(s):  
Sotiris Kyriakou ◽  
William Cheung ◽  
Theodora Mantso ◽  
Melina Mitsiogianni ◽  
Ioannis Anestopoulos ◽  
...  

SummaryMelanoma is an aggressive and highly metastatic type of skin cancer where the design of new therapies is of utmost importance for the clinical management of the disease. Thus, we have aimed to investigate the mode of action by which a novel methylated analogue of L-Mimosine (e.g., L-SK-4) exerts its therapeutic potency in an in vitro model of malignant melanoma. Cytotoxicity was assessed by the Alamar Blue assay, oxidative stress by commercially available kits, ROS generation, caspase 3/7 activation and mitochondrial membrane depolarisation by flow cytometry, expression of apoptosis-related proteins by western immunoblotting and profiling of lipid biosynthesis by a metabolomic approach. Overall, higher levels of ROS, sphingolipids and apoptosis were induced by L-SK-4 suggesting that the compound’s therapeutic potency is mediated through elevated ROS levels which promote the upregulation of sphingolipid (ceramide) biosynthesis thus leading to the activation of both extrinsic and intrinsic apoptosis, in an experimental model of malignant melanoma.


1984 ◽  
Vol 25 (3) ◽  
pp. 215-224 ◽  
Author(s):  
NOBUO KUBOTA ◽  
KENGO MATSUI ◽  
SHINICHIRO SATO ◽  
TETSUO INADA

Planta Medica ◽  
2018 ◽  
Vol 85 (02) ◽  
pp. 118-125 ◽  
Author(s):  
Iwona Stanisławska ◽  
Sebastian Granica ◽  
Jakub Piwowarski ◽  
Joanna Szawkało ◽  
Krzysztof Wiązecki ◽  
...  

AbstractThe gut microbiota-derived metabolites of ellagitannins and green tea catechins, urolithin A (uroA) and 5-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone (M4), respectively, are among the main compounds absorbed into human system after ingestion of these polyphenols. The aim of this study was to establish the effects of M4, uroA, and their combinations on LNCaP cells, an androgen dependent prostate cancer in vitro model.. The LNCaP cells were incubated with increasing concentrations of tested metabolites. The cell proliferation was determined by measurement of DNA-bisbenzimide H 33 258 complexes fluorescence. The isobolographic analysis was used to establish the type of interaction between metabolites. The apoptosis, androgen receptor (AR) localization, and phosphorylation of Akt kinase were measured by flow cytometry. Prostate-specific antigen (PSA) secretion was determined by ELISA. M4 showed modest antiproliferative activity in LNCaP cells (IC50 = 117 µM; CI: 81 – 154). UroA decreased proliferation (IC50 = 32.7 µM; CI: 24.3 – 41.1) and induced apoptosis of LNCaP cells. The mixture of M4 with uroA had synergistic antiproliferative effect. Moreover, M4 potentiated inhibition of PSA secretion and enhanced retention of AR in cytoplasm caused by uroA. Interestingly, uroA increased levels of pSer473 Akt in LNCaP cells. These results show that colonic metabolites may contribute to chemoprevention of prostate cancer by varied polyphenol-rich diet or composite polyphenol preparations.


1989 ◽  
Vol 11 (3) ◽  
pp. 285
Author(s):  
A. Majid ◽  
P. W.M. Copeman ◽  
K. Henry

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