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[ CAS No. 50-63-5 ] {[proInfo.proName]}

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Chemical Structure| 50-63-5
Chemical Structure| 50-63-5
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Perez, Celia N. ; Falcon, Cristian R. ; Mons, Johinna Delgado , et al. DOI: PubMed ID:

Abstract: Over the last years, the incidence of melanoma, the deadliest form of skin cancer, has risen significantly. Nearly half of the melanoma patients exhibit the BRAFV600E mutation. Although the use of BRAF and MEK inhibitors (BRAFi and MEKi) showed an impressive success rate in melanoma patients, durability of response remains an issue because tumor quickly becomes resistant. Here, we generated and characterized Lu1205 and A375 melanoma cells resistant to vemurafenib (BRAFi). Resistant cells (Lu1205R and A375R) exhibit higher IC50 (5-6 fold increase) and phospho-ERK levels and 2-3 times reduced apoptosis than their sensitive parents (Lu1205S and A375S). Moreover, resistant cells are 2-3 times bigger, display a more elongated morphol. and have a modulation of migration capacity. Interestingly, pharmacol. inhibition of sphingosine kinases, that prevents sphingosine-1-phosphate production, reduces migration of Lu1205R cells by 50%. In addition, although Lu1205R cells showed increased basal levels of the autophagy markers LC3II and p62, they have decreased autophagosome degradation and autophagy flux. Remarkably, expression of Rab27A and Rab27B, which are involved in the release of extracellular vesicles are dramatically augmented in resistant cells (i.e. 5-7 fold increase). Indeed, conditioned media obtained from Lu1205R cells increased the resistance to vemurafenib of sensitive cells. Hence, these results support that resistance to vemurafenib modulates migration and the autophagic flux and may be transferred to nearby sensitive melanoma cells by factors that are released to the extracellular milieu by resistant cells.

Keywords: Melanoma ; BRAF V600E mutation ; Vemurafenib ; Autophagy ; Resistance transfer

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Product Details of [ 50-63-5 ]

CAS No. :50-63-5 MDL No. :MFCD00069852
Formula : C18H32ClN3O8P2 Boiling Point : -
Linear Structure Formula :- InChI Key :QKICWELGRMTQCR-UHFFFAOYSA-N
M.W : 515.86 Pubchem ID :64927
Synonyms :
Chloroquine (phosphate) (CRM);Chloroquine diphosphate;NSC 14050;DL-Chloroquine
Chemical Name :N4-(7-Chloroquinolin-4-yl)-N1,N1-diethylpentane-1,4-diamine bis(phosphate)

Safety of [ 50-63-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
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