scholarly journals Involvement of Mitochondrial Mechanisms in the Cytostatic Effect of Desethylamiodarone in B16F10 Melanoma Cells

2020 ◽  
Vol 21 (19) ◽  
pp. 7346
Author(s):  
Fadi H. J. Ramadan ◽  
Aliz Szabo ◽  
Dominika Kovacs ◽  
Aniko Takatsy ◽  
Rita Bognar ◽  
...  

Previously, we showed that desethylamiodarone (DEA), a major metabolite of the widely used antiarrhythmic drug amiodarone, has direct mitochondrial effects. We hypothesized that these effects account for its observed cytotoxic properties and ability to limit in vivo metastasis. Accordingly, we examined DEA’s rapid (3–12 h) cytotoxicity and its early (3–6 h) effects on various mitochondrial processes in B16F10 melanoma cells. DEA did not affect cellular oxygen radical formation, as determined using two fluorescent dyes. However, it did decrease the mitochondrial transmembrane potential, as assessed by JC-1 dye and fluorescence microscopy. It also induced mitochondrial fragmentation, as visualized by confocal fluorescence microscopy. DEA decreased maximal respiration, ATP production, coupling efficiency, glycolysis, and non-mitochondrial oxygen consumption measured by a Seahorse cellular energy metabolism analyzer. In addition, it induced a cyclosporine A–independent mitochondrial permeability transition, as determined by Co2+-mediated calcein fluorescence quenching measured using a high-content imaging system. DEA also caused outer mitochondrial membrane permeabilization, as assessed by the immunoblot analysis of cytochrome C, apoptosis inducing factor, Akt, phospho-Akt, Bad, and phospho-Bad. All of these data supported our initial hypothesis.

2018 ◽  
Vol 283 ◽  
pp. 10-19 ◽  
Author(s):  
Aïcha Sassi ◽  
Mouna Maatouk ◽  
Dorra El gueder ◽  
Imen Mokdad Bzéouich ◽  
Saïda Abdelkefi-Ben Hatira ◽  
...  

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 808 ◽  
Author(s):  
Inès Dufait ◽  
Julian Pardo ◽  
David Escors ◽  
Yannick De Vlaeminck ◽  
Heng Jiang ◽  
...  

A wide-range of myeloid-derived suppressor cell (MDSC)-mediated immune suppressive functions has previously been described. Nevertheless, potential novel mechanisms by which MDSCs aid tumor progression are, in all likelihood, still unrecognized. Next to its well-known expression in natural killer cells and cytotoxic T lymphocytes (CTLs), granzyme B (GzmB) expression has been found in different cell types. In an MDSC culture model, we demonstrated perforin and GzmB expression. Furthermore, similar observations were made in MDSCs isolated from tumor-bearing mice. Even in MDSCs from humans, GzmB expression was demonstrated. Of note, B16F10 melanoma cells co-cultured with perforin/GzmB knock out mice (KO) MDSCs displayed a remarkable decrease in invasive potential. B16F10 melanoma cells co-injected with KO MDSCs, displayed a significant slower growth curve compared to tumor cells co-injected with wild type (WT) MDSCs. In vivo absence of perforin/GzmB in MDSCs resulted in a higher number of CD8+ T-cells. Despite this change in favor of CD8+ T-cell infiltration, we observed low interferon-γ (IFN-γ) and high programmed death-ligand 1 (PD-L1) expression, suggesting that other immunosuppressive mechanisms render these CD8+ T-cells dysfunctional. Taken together, our results suggest that GzmB expression in MDSCs is another means to promote tumor growth and warrants further investigation to unravel the exact underlying mechanism.


2019 ◽  
Vol 62 (1) ◽  
Author(s):  
Hwang-Ju Jeon ◽  
Kyeongnam Kim ◽  
Yong-Deuk Kim ◽  
Sung-Eun Lee

Abstract In this study, the antimelanogenic activity of piperlongumine in murine B16F10 melanoma cells and zebrafish was investigated, and its mode of antimelanogenic action was elucidated using quantitative reverse transcription-polymerase chain reaction. A melanocyte-stimulating hormone (α-MSH, 200 nM) was used to induce melanin production in B16F10 melanoma cells, and kojic acid (200 μM) was used as a positive control. Piperlongumine had no inhibitory effects on cell growth at the treated concentrations (3 and 6 μM), and it significantly reduced total melanin production. Piperlongumine decreased the expression of Mitf, Tyr, Trp-1, and Trp-2 and tyrosinase activity was also dramatically reduced by the piper amide addition under α-MSH treatment. With these findings, zebrafish embryos were used to confirm antimelanogenic activity of piperlongumine, and it showed the potent antimelanogenic activity at the concentration of 1 μM. Altogether, piperlongumine has potent antimelanogenic activity, and these results support it as a candidate for natural depigmentation agent in a cosmetic and pharmaceutical industries.


2016 ◽  
Vol 12 (3) ◽  
pp. 69-76
Author(s):  
Arax Tanelian ◽  
Dalal F. Jaber ◽  
Nayla S. Al Akl ◽  
Alexander M. Abdelnoor

2013 ◽  
Vol 31 (2) ◽  
pp. 819-827 ◽  
Author(s):  
PATRYCJA KOSZAŁKA ◽  
ANNA PRYSZLAK ◽  
MONIKA GOŁUŃSKA ◽  
JUSTYNA KOLASA ◽  
GRZEGORZ STASIŁOJĆ ◽  
...  

1994 ◽  
Vol 120 (11) ◽  
pp. 631-635 ◽  
Author(s):  
Tatsuo Ohira ◽  
Yuichiro Ohe ◽  
Yuji Heike ◽  
Eckhard R. Podack ◽  
Kristin J. Olsen ◽  
...  

2013 ◽  
Vol 15 (11) ◽  
pp. 1197-1203 ◽  
Author(s):  
Sumana Mallick ◽  
Bikas Chandra Pal ◽  
Deepak Kumar ◽  
Nabanita Chatterjee ◽  
Subhadip Das ◽  
...  

2017 ◽  
Vol 46 (1) ◽  
pp. 34-38
Author(s):  
Hyang Suk Kim ◽  
Ji Min Cheon ◽  
Da Hye Kwon ◽  
Eun Ok Choi ◽  
Min Ju Kim ◽  
...  

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