Chemical Research in Toxicology, Volume (32), No (4), Year (2019-4) , Pages (645-658)

Title : ( Concentration-Dependent Dual Effects of Ciprofloxacin on SB-590885-Resistant BRAFV600E A375 Melanoma Cells )

Authors: Seyyede Araste Aldaghi , Razieh Jalal ,

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Abstract

BRAF inhibitors -BRAFi- have been applied to treat melanoma harboring V600E mutations. Several studies showed that BRAFi-resistant melanomas are dependent on mitochondrial biogenesis. Therefore, the present study aimed to investigate the influence of ciprofloxacin -CIP-, a mitochondria-targeting antibiotic, on SB-590885-resistant BRAFV600E A375 melanoma -A375/SB- cells. The cytotoxicity activity of CIP and SB-590885, a potent and specific BRAFi, on A375 and A375/SB cells was evaluated by MTT, colony formation, migration and spheroid formation assays. Moreover, SB-590885-induced cell death in A375 cells was analyzed. SB-590885 showed time- and concentration-dependent cytotoxic effects on A375 cells. 25 μg/mL CIP decreased the cell viability of A375 and A375/SB cells in a time-dependent manner. This concentration of CIP markedly decreased clonogenicity in both cells and caused a reduction in the growth of A375/SB spheroids. The cytotoxicity of 5 μg/mL CIP on A375/SB cells was less than that of A375 cells. The colony formation and migration ability of A375/SB cells was increased in the presence of 5 μg/mL CIP. 10 μM SB-590885 induced a massive vacuolization in A375 cells. Cell death assays suggested a simultaneous activation of autophagy, paraptosis, apoptosis and necrosis. For the first time, this study reveals that CIP at the maximum concentration in serum -5 μg/mL- can enhance the colony formation and migration abilities in BRAFi-resistant melanoma cells while it has cytotoxic activity against these cells at a higher concentration than serum level. This study suggests that CIP may promote aggressive growth properties in BRAFi-resistant melanomas, at a concentration present in serum.

Keywords

, A375; Ciprofloxacin; BRAFV600E inhibitor; BRAFi, resistant melanomas; SB, 590885
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@article{paperid:1073823,
author = {Aldaghi, Seyyede Araste and Jalal, Razieh},
title = {Concentration-Dependent Dual Effects of Ciprofloxacin on SB-590885-Resistant BRAFV600E A375 Melanoma Cells},
journal = {Chemical Research in Toxicology},
year = {2019},
volume = {32},
number = {4},
month = {April},
issn = {0893-228X},
pages = {645--658},
numpages = {13},
keywords = {A375; Ciprofloxacin; BRAFV600E inhibitor; BRAFi-resistant melanomas; SB-590885},
}

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%0 Journal Article
%T Concentration-Dependent Dual Effects of Ciprofloxacin on SB-590885-Resistant BRAFV600E A375 Melanoma Cells
%A Aldaghi, Seyyede Araste
%A Jalal, Razieh
%J Chemical Research in Toxicology
%@ 0893-228X
%D 2019

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