Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis
Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis
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DOI：
10.1042/bj20150122
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发表时间：
2015-07-15
影响因子：
4.1
通讯作者：
Steinberg, Gregory R.
中科院分区：
文献类型：
--
作者：
O'Brien, Andrew J.;Villani, Linda A.;Steinberg, Gregory R.
阿司匹林是水杨酸盐的前体药物，与结肠癌、肺癌和前列腺癌的死亡率降低有关，通常与二甲双胍联合用于2型糖尿病患者。水杨酸盐通过结合AMPK β 1亚基上的A-769662药物结合位点激活AMPK，这一机制与破坏细胞腺苷酸电荷的二甲双胍不同。许多癌症的标志是脂肪酸合成的高速率，AMPK通过乙酰辅酶A羧化酶（ACC）的磷酸化来抑制该途径。目前尚不清楚使用水杨酸盐和/或二甲双胍靶向AMPK-ACC-脂肪生成途径是否可有效抑制癌细胞存活。水杨酸盐抑制前列腺癌和肺癌细胞在服用阿司匹林后达到的治疗浓度下的克隆形成存活（
Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK beta 1-subunit, amechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (