Oncotarget 2015-06-30

Redox effects and cytotoxic profiles of MJ25 and auranofin towards malignant melanoma cells.

Marijke C C Sachweh, William C Stafford, Catherine J Drummond, Anna R McCarthy, Maureen Higgins, Johanna Campbell, Bertha Brodin, Elias S J Arnér, Sonia Laín

文献索引:Oncotarget 6 , 16488-506, (2015)

全文:HTML全文

摘要

Malignant melanoma is the most dangerous type of skin cancer. Although recent progress in treatment has been achieved, lack of response, drug resistance and relapse remain major problems. The tumor suppressor p53 is rarely mutated in melanoma, yet it is inactive in the majority of cases due to dysregulation of upstream pathways. Thus, we screened for compounds that can activate p53 in melanoma cells. Here we describe effects of the small molecule MJ25 (2-{[2-(1,3-benzothiazol-2-ylsulfonyl)ethyl]thio}-1,3-benzoxazole), which increased the level of p53-dependent transactivation both as a single agent and in combination with nutlin-3. Furthermore, MJ25 showed potent cytotoxicity towards melanoma cell lines, whilst having weaker effects against human normal cells. MJ25 was also identified in an independent screen as an inhibitor of thioredoxin reductase 1 (TrxR1), an important selenoenzyme in the control of oxidative stress and redox regulation. The well-characterized TrxR inhibitor auranofin, which is FDA-approved and currently in clinical trials against leukemia and a number of solid cancers, displayed effects comparable with MJ25 on cells and led to eradication of cultured melanoma cells at low micromolar concentrations. In conclusion, auranofin, MJ25 or other inhibitors of TrxR1 should be evaluated as candidate compounds or leads for targeted therapy of malignant melanoma.


相关化合物

  • 溴化乙啶
  • 丙酮
  • 盐酸
  • 甲醇
  • N,N'-二甲基乙二胺
  • 磷酸氢二钠
  • 5,5'二硫代双(2-硝...
  • 三氯乙酸钠
  • 二甲基亚砜
  • 胡桃酮,5-羟基对萘...

相关文献:

L. monocytogenes in a cheese processing facility: Learning from contamination scenarios over three years of sampling.

2014-10-17

[Int. J. Food Microbiol. 189 , 98-105, (2014)]

Alpha-fetoprotein, identified as a novel marker for the antioxidant effect of placental extract, exhibits synergistic antioxidant activity in the presence of estradiol.

2014-01-01

[PLoS ONE 9(6) , e99421, (2014)]

Vegetables' juice influences polyol pathway by multiple mechanisms in favour of reducing development of oxidative stress and resultant diabetic complications.

2014-04-01

[Pharmacogn. Mag. 10(Suppl 2) , S383-91, (2014)]

Glucose recognition proteins for glucose sensing at physiological concentrations and temperatures.

2014-07-18

[ACS Chem. Biol. 9(7) , 1595-602, (2014)]

Reservoirs of listeria species in three environmental ecosystems.

2014-09-01

[Appl. Environ. Microbiol. 80(18) , 5583-92, (2014)]

更多文献...