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活性氧:癌症生存的关键成分

Reactive Oxygen Species: A Key Constituent in Cancer Survival.

作者信息

Kumari Seema, Badana Anil Kumar, G Murali Mohan, G Shailender, Malla RamaRao

机构信息

Cancer Biology Lab, Department of Biochemistry, GIS, GITAM (Deemed to be University), Visakhapatnam, India.

出版信息

Biomark Insights. 2018 Feb 6;13:1177271918755391. doi: 10.1177/1177271918755391. eCollection 2018.

Abstract

BACKGROUND

Cancer is one of the major heterogeneous disease with high morbidity and mortality with poor prognosis. Elevated levels of reactive oxygen species (ROS), alteration in redox balance, and deregulated redox signaling are common hallmarks of cancer progression and resistance to treatment. Mitochondria contribute mainly in the generation of ROS during oxidative phosphorylation. Elevated levels of ROS have been detected in cancers cells due to high metabolic activity, cellular signaling, peroxisomal activity, mitochondrial dysfunction, activation of oncogene, and increased enzymatic activity of oxidases, cyclooxygenases, lipoxygenases, and thymidine phosphorylases. Cells maintain intracellular homeostasis by developing an immense antioxidant system including catalase, superoxide dismutase, and glutathione peroxidase. Besides these enzymes exist an important antioxidant glutathione and transcription factor Nrf2 which contribute in balancing oxidative stress. Reactive oxygen species-mediated signaling pathways activate pro-oncogenic signaling which eases in cancer progression, angiogenesis, and survival. Concomitantly, to maintain ROS homeostasis and evade cancer cell death, an increased level of antioxidant capacity is associated with cancer cells.

CONCLUSIONS

This review focuses the role of ROS in cancer survival pathways and importance of targeting the ROS signal involved in cancer development, which is a new strategy in cancer treatment.

摘要

背景

癌症是主要的异质性疾病之一,发病率和死亡率高,预后差。活性氧(ROS)水平升高、氧化还原平衡改变以及氧化还原信号失调是癌症进展和治疗耐药的常见特征。线粒体在氧化磷酸化过程中主要参与ROS的产生。由于高代谢活性、细胞信号传导、过氧化物酶体活性、线粒体功能障碍、癌基因激活以及氧化酶、环氧化酶、脂氧化酶和胸苷磷酸化酶的酶活性增加,癌细胞中已检测到ROS水平升高。细胞通过发展包括过氧化氢酶、超氧化物歧化酶和谷胱甘肽过氧化物酶在内的庞大抗氧化系统来维持细胞内稳态。除了这些酶,还存在重要的抗氧化剂谷胱甘肽和转录因子Nrf2,它们有助于平衡氧化应激。活性氧介导的信号通路激活促癌信号,这有助于癌症进展、血管生成和存活。与此同时,为了维持ROS稳态并逃避癌细胞死亡,癌细胞的抗氧化能力水平升高。

结论

本综述重点关注ROS在癌症生存途径中的作用以及靶向参与癌症发展的ROS信号的重要性,这是癌症治疗的一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fa3/5808965/37ecd70869a5/10.1177_1177271918755391-fig1.jpg

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