Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype
Mimicry of a cellular low energy status blocks tumor cell anabolism and suppresses the malignant phenotype
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DOI：
10.1158/0008-5472.can-04-3025
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发表时间：
2005-03-15
期刊：
影响因子：
11.2
通讯作者：
Verhoeven, G
中科院分区：
文献类型：
--
作者：
Swinnen, JV;Beckers, A;Verhoeven, G
侵袭性癌细胞通常表现出高耗能的合成代谢过程，推动脂质、蛋白质和DNA的合成。在这里，我们利用细胞渗透性核苷5-氨基咪唑-4-甲酰胺(AICA)核苷的能力来增加细胞内AMP类似物AICA核糖肽的水平，模拟细胞的低能量状态。用AICA核苷治疗癌细胞会阻碍脂肪生成，减少蛋白质翻译，并阻止DNA合成。经AICA核苷处理的细胞停止增殖，失去侵袭特性和形成集落的能力。体内给药时，AICA核苷可抑制裸鼠体内MDA-MB-231肿瘤的生长。这些发现指出了能量、合成代谢和癌症之间的中心联系，并表明癌细胞中的细胞能量感应机制是癌症预防和/或治疗的可利用的目标。
Aggressive cancer cells typically show a high rate of energy-consuming anabolic processes driving the synthesis of lipids, proteins, and DNA. Here, we took advantage of the ability of the cell-permeable nucleoside 5-aminoimidazole-4-carboxamide (AICA) riboside to increase the intracellular levels of AICA ribotide, an AMP analogue, mimicking a low energy status of the cell. Treatment of cancer cells with AICA riboside impeded lipogenesis, decreased protein translation, and blocked DNA synthesis. Cells treated with AICA riboside stopped proliferating and lost their invasive properties and their ability to form colonies. When administered in vivo, AICA riboside attenuated the growth of MDA-MB-231 tumors in nude mice. These findings point toward a central tie between energy, anabolism, and cancer and suggest that the cellular energy sensing machinery in cancer cells is an exploitable target for cancer prevention and/or therapy.