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首页> 外文期刊>The FEBS journal >Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation
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Essential amino acid mixtures drive cancer cells to apoptosis through proteasome inhibition and autophagy activation

机译：基本氨基酸混合物通过蛋白酶体抑制和自噬激活将癌细胞驱动到细胞凋亡

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摘要

Cancer cells require both energy and material to survive and duplicate in a competitive environment. Nutrients, such as amino acids (AAs), are not only a caloric source, but can also modulate cell metabolism and modify hormone homeostasis. Our hypothesis is that the environmental messages provided by AAs rule the dynamics of cancer cell life or death, and the alteration of the balance between essential amino acids (EAAs) and nonessential amino acids (NEAAs) (lower and higher than 50%, respectively) present in nutrients may represent a key instrument to alter environment-dependent messages, thus mastering cancer cells destiny. In this study, two AA mixtures, one exclusively consisting of EAAs and the other consisting of 85% EAAs and 15% NEAAs, were tested to explore their effects on the viability of both normal and cancer cell lines and to clarify the molecular mechanisms involved. Both mixtures exerted a cell-dependent anti-proliferative, cytotoxic effect involving the inhibition of proteasome activity and the consequent activation of autophagy and apoptosis. These results, besides further validating the notion of the peculiar interdependence and extensive crosstalk between the ubiquitin-proteasome system (UPS) and autophagy, indicate that variation in the ratio of EAAs and NEAAs can deeply influence cancer cell survival. Consequently, customization of dietary ratios among EAAs and NEAAs by specific AA mixtures may represent a promising anticancer strategy able to selectively induce death of cancer cells through the induction of apoptosis via both UPS inhibition and autophagy activation.
机译：癌细胞需要能源和材料的生存和竞争环境中复制。营养物，如氨基酸（AAS），这样不仅是一个热量源，但也可以调节细胞代谢和修改激素动态平衡。我们的假设是由AA提供的环境信息排除癌细胞生命或死亡，和必需氨基酸（必需氨基酸）和非必需氨基酸（NEAAs）之间的平衡的改变的动力学（降低和高于50％，分别地）存在于营养物可以代表一个重要手段，以改变依赖于环境的信息，从而掌握癌细胞的命运。在这项研究中，两分AA的混合物，一个只由必需氨基酸的组成，另一个由85周％的EAA和15个％NEAAs的，进行测试，以探索对正常和癌细胞系的生存力的影响，并澄清所涉及的分子机制。两种混合物施加涉及蛋白酶活性的抑制和自噬和凋亡的后续活化一个依赖性细胞的抗增殖，细胞毒性作用。这些结果，除了进一步验证特有相互依赖和泛素 - 蛋白酶体系统（UPS）和自噬之间的广泛的串扰的概念，指示必需氨基酸的比例的变异和NEAAs可以深刻影响癌症细胞的存活。因此，必需氨基酸和NEAAs之间膳食比由特定AA混合物的定制可以表示能够选择性地通过经由两个UPS抑制和自体吞噬的活化诱导细胞凋亡诱导癌细胞死亡的有前途的抗癌策略。

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