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A potentiated cooperation of carbonic anhydrase IX and histone deacetylase inhibitors against cancer.
Journal of Enzyme inhibition and Medicinal Chemistry ( IF 5.6 ) Pub Date : 2019-12-22 , DOI: 10.1080/14756366.2019.1706090
Jessica Ruzzolini 1 , Anna Laurenzana 1 , Elena Andreucci 1 , Silvia Peppicelli 1 , Francesca Bianchini 1 , Fabrizio Carta 2 , Claudiu T Supuran 2 , Maria Novella Romanelli 2 , Chiara Nediani 1 , Lido Calorini 1, 3
Affiliation  

The emergence of tumour recurrence and resistance limits the survival rate for most tumour-bearing patients. Only, combination therapies targeting pathways involved in the induction and in the maintenance of cancer growth and progression might potentially result in an enhanced therapeutic efficacy. Herein, we provided a prospective combination treatment that includes suberoylanilide hydroxamic acid (SAHA), a well-known inhibitor of histone deacetylases (HDACs), and SLC-0111, a novel inhibitor of carbonic anhydrase (CA) IX. We proved that HDAC inhibition with SAHA in combination with SLC-0111 affects cell viability and colony forming capability to greater extent than either treatment alone of breast, colorectal and melanoma cancer cells. At the molecular level, this therapeutic regimen resulted in a synergistically increase of histone H4 and p53 acetylation in all tested cell lines. Overall, our findings showed that SAHA and SLC-0111 can be regarded as very attractive combination providing a potential therapeutic strategy against different cancer models.

中文翻译:

碳酸酐酶 IX 和组蛋白脱乙酰酶抑制剂在抗癌方面的强效合作。

肿瘤复发和耐药的出现限制了大多数荷瘤患者的生存率。只是,针对癌症生长和进展的诱导和维持途径的联合疗法可能会增强治疗效果。在此,我们提供了一种前瞻性联合治疗,包括辛二酰苯胺异羟肟酸(SAHA)(一种著名的组蛋白脱乙酰酶(HDAC)抑制剂)和SLC-0111(一种新型碳酸酐酶(CA)IX抑制剂)。我们证明,与单独治疗乳腺癌、结直肠癌和黑色素瘤癌细胞相比,SAHA 与 SLC-0111 联合抑制 HDAC 对细胞活力和集落形成能力的影响更大。在分子水平上,这种治疗方案导致所有测试细胞系中组蛋白 H4 和 p53 乙酰化协同增加。总的来说,我们的研究结果表明 SAHA 和 SLC-0111 可以被视为非常有吸引力的组合,为不同的癌症模型提供了潜在的治疗策略。
更新日期:2020-04-20
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