Ferraresi Alessandra, Titone Rossella, Follo Carlo, Castiglioni Andrea, Chiorino Giovanna, Dhanasekaran Danny N, Isidoro Ciro
Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale "A. Avogadro", Novara, Italy.
Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia, Biella, Italy.
Mol Carcinog. 2017 Dec;56(12):2681-2691. doi: 10.1002/mc.22711. Epub 2017 Sep 7.
The potential benefit of nutrient starvation in the prevention and treatment of cancer is presently under consideration. Resveratrol (RV), a dietary polyphenol acting as a protein (caloric) restriction mimetic, could substitute for amino acid starvation. The effects of starvation and of caloric restriction are mediated, among others, by autophagy, a process that contributes to cell homeostasis by promoting the lysosomal degradation of damaged and redundant self-constituents. Up-regulation of autophagy favors cell survival under nutrient shortage situation, and may drive cancer cells into a non-replicative, dormant state. Both RV and amino acid starvation effectively induced the aminoacid response and autophagy. These processes were associated with inhibition of the mTOR pathway and disruption of the BECLIN1-BCL-2 complex. The number of transcripts positively impinging on the autophagy pathway was higher in RV-treated than in starved cancer cells. Consistent with our data, it appears that RV treatment is more effective than and can substitute for starvation for inducing autophagy in cancer cells. The present findings are clinically relevant because of the potential therapeutic implications.
目前正在探讨营养饥饿在癌症预防和治疗中的潜在益处。白藜芦醇（RV）是一种膳食多酚，可模拟蛋白质（热量）限制，能够替代氨基酸饥饿。饥饿和热量限制的作用，除其他外，由自噬介导，自噬是一个通过促进受损和多余自身成分的溶酶体降解来维持细胞稳态的过程。自噬的上调有利于细胞在营养短缺情况下存活，并可能使癌细胞进入非复制性休眠状态。RV和氨基酸饥饿均能有效诱导氨基酸反应和自噬。这些过程与mTOR通路的抑制以及BECLIN1 - BCL - 2复合物的破坏有关。与饥饿的癌细胞相比，RV处理的癌细胞中正向影响自噬途径的转录本数量更多。与我们的数据一致，似乎RV处理在诱导癌细胞自噬方面比饥饿更有效且可替代饥饿。由于其潜在的治疗意义，目前的研究结果具有临床相关性。
