Rahman Md Ataur, Ahmed Kazi Rejvee, Haque Farzana, Park Moon Nyeo, Kim Bonglee
Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul 02447, Republic of Korea.
Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Antioxidants (Basel). 2023 Feb 9;12(2):428. doi: 10.3390/antiox12020428.
Autophagy is a fundamental homeostatic process in which certain cellular components are ingested by double-membrane autophagosomes and then degraded to create energy or to maintain cellular homeostasis and survival. It is typically observed in nutrient-deprived cells as a survival mechanism. However, it has also been identified as a crucial process in maintaining cellular homeostasis and disease progression. Normal cellular metabolism produces reactive oxygen (ROS) and nitrogen species at low levels. However, increased production causes oxidative stress, which can lead to diabetes, cardiovascular diseases, neurological disorders, and cancer. It was recently shown that maintaining redox equilibrium via autophagy is critical for cellular responses to oxidative stress. However, little is understood about the molecular cancer processes that connect to the control of autophagy. In cancer cells, oncogenic mutations, carcinogens, and metabolic reprogramming cause increased ROS generation and oxidative stress. Recent studies have suggested that increased ROS generation activates survival pathways that promote cancer development and metastasis. Moreover, the relationship between metabolic programming and ROS in cancer cells is involved in redox homeostasis and the malignant phenotype. Currently, while the signaling events governing autophagy and how redox homeostasis affects signaling cascades are well understood, very little is known about molecular events related to autophagy. In this review, we focus on current knowledge about autophagy modulation and the role of redox metabolism to further the knowledge of oxidative stress and disease progression in cancer regulation. Therefore, this review focuses on understanding how oxidation/reduction events fine-tune autophagy to help understand how oxidative stress and autophagy govern cancer, either as processes leading to cell death or as survival strategies for maintaining redox homeostasis in cancer.
自噬是一种基本的稳态过程，在该过程中某些细胞成分被双膜自噬体摄取，然后被降解以产生能量或维持细胞稳态及存活。自噬通常在营养缺乏的细胞中作为一种存活机制被观察到。然而，它也被认为是维持细胞稳态和疾病进展的关键过程。正常细胞代谢会产生低水平的活性氧（ROS）和氮化物。然而，其产量增加会导致氧化应激，进而可能引发糖尿病、心血管疾病、神经紊乱和癌症。最近有研究表明，通过自噬维持氧化还原平衡对于细胞应对氧化应激至关重要。然而，对于与自噬控制相关的分子致癌过程却知之甚少。在癌细胞中，致癌突变、致癌物和代谢重编程会导致ROS生成增加和氧化应激。最近的研究表明，ROS生成增加会激活促进癌症发展和转移的存活途径。此外，癌细胞中代谢编程与ROS之间的关系涉及氧化还原稳态和恶性表型。目前，虽然调控自噬的信号事件以及氧化还原稳态如何影响信号级联已为人熟知，但对于与自噬相关的分子事件却知之甚少。在本综述中，我们聚焦于自噬调节的现有知识以及氧化还原代谢的作用，以进一步了解癌症调控中氧化应激和疾病进展的相关知识。因此，本综述着重于理解氧化/还原事件如何微调自噬，以帮助理解氧化应激和自噬如何控制癌症，无论是作为导致细胞死亡的过程还是作为维持癌症氧化还原稳态的存活策略。
