Institute of Food Sciences, National Research Council, 83100 Avellino, Italy.
Institute of Food Sciences, National Research Council, 83100 Avellino, Italy.
Biochem Pharmacol. 2018 Jul;153:51-61. doi: 10.1016/j.bcp.2018.02.007. Epub 2018 Feb 10.
Autophagy is a complex, physiological process devoted to degrade and recycle cellular components. Proteins and organelles are first phagocytized by autophagosomes, then digested in lysosomes, and finally recycled to be utilized again during cellular metabolism. Moreover, autophagy holds an important role in the physiopathology of several diseases. In cancer, excellent works demonstrated the dual functions of autophagy in tumour biology: autophagy activation can promote cancer cells survival (protective autophagy), or contribute to cancer cell death (cytotoxic/nonprotective autophagy). A better understanding of the dichotomy roles of autophagy in cancer biology can help to identify or design new drugs able to induce/enhance (or block) autophagic flux. These features will necessary be tissue-dependent and confined to a specific time of treatment. The intent of this review is to focus on the different potentialities of autophagy inducers in cancer prevention versus therapy in order to elicit a desirable clinical response. Few promising synthetic and natural compounds have been identified and the pros and cons of their role in autophagy regulation is reviewed here. In the complex framework of autophagy modulation, "connecting the dots" is not a simple work and the lack of clinical studies further complicates the scenario, but the final goal to obtain clinically relevant autophagy inducers can reveal an unexpected landscape.
自噬是一种复杂的生理过程，致力于降解和回收细胞成分。蛋白质和细胞器首先被自噬体吞噬，然后在溶酶体中消化，最后在细胞代谢过程中回收再利用。此外，自噬在几种疾病的病理生理学中起着重要作用。在癌症中，优秀的工作证明了自噬在肿瘤生物学中的双重功能：自噬的激活可以促进癌细胞的存活（保护性自噬），或有助于癌细胞死亡（细胞毒性/非保护性自噬）。更好地理解自噬在癌症生物学中的双重作用，可以帮助识别或设计能够诱导/增强（或阻断）自噬通量的新药物。这些特性将取决于组织，并局限于特定的治疗时间。本综述的目的是集中讨论自噬诱导剂在癌症预防与治疗中的不同潜力，以引起理想的临床反应。已经确定了一些有前途的合成和天然化合物，并在此审查了它们在自噬调节中的利弊。在自噬调节的复杂框架中，“连接点”并不是一件简单的工作，缺乏临床研究进一步使情况复杂化，但获得具有临床相关性的自噬诱导剂的最终目标可以揭示出意想不到的前景。
