Redox regulation in cancer: a double-edged sword with therapeutic potential.
Redox regulation in cancer: a double-edged sword with therapeutic potential.
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DOI：
10.4161/oxim.3.1.10095
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发表时间：
2010-01
影响因子：
--
通讯作者：
Saha T
中科院分区：
文献类型：
--
作者：
Acharya A;Das I;Chandhok D;Saha T
氧化应激与癌症的病因学有关，是由活性氧（ROS）的产生和细胞自身的抗氧化防御失衡引起的。ROS通过引发导致肿瘤发生的信号网络的异常诱导来解除氧化还原稳态并促进肿瘤形成。紫外线、γ射线等环境致癌物在细胞内产生活性氧，通过阻断细胞防御系统，使肿瘤细胞凋亡，从而杀死恶性肿瘤细胞或诱导肿瘤生长。癌症干细胞利用异常的氧化还原系统并自发增殖。氧化应激和基因-环境相互作用在乳腺癌、前列腺癌、胰腺癌和结肠癌的发展中起着重要作用。长期接触雌激素与几种DNA损伤有关。氧化应激和雌激素受体相关的增殖性改变在雌激素诱导的乳腺癌发生中起重要作用。BRCA 1是一种针对激素反应性癌症（如乳腺癌和前列腺癌）的肿瘤抑制因子，在抑制ROS和雌激素介导的DNA损伤中起重要作用;从而调节细胞的氧化还原稳态。在应激反应过程中涉及多种转录因子和肿瘤抑制因子，如Nrf 2、NFκB和BRCA 1。靶向细胞氧化还原状态的一个有前途的策略是使用来自蔬菜、水果、草药和香料的容易获得的天然物质。许多植物化学物质已被确定具有化学预防潜力，能够干预致癌作用。
Oxidative stress, implicated in the etiology of cancer, results from an imbalance in the production of reactive oxygen species (ROS) and cell’s own antioxidant defenses. ROS deregulate the redox homeostasis and promote tumor formation by initiating an aberrant induction of signaling networks that cause tumorigenesis. Ultraviolet (UV) exposures, γ-radiation and other environmental carcinogens generate ROS in the cells, which can exert apoptosis in the tumors, thereby killing the malignant cells or induce the progression of the cancer growth by blocking cellular defense system. Cancer stem cells take the advantage of the aberrant redox system and spontaneously proliferate. Oxidative stress and gene-environment interactions play a significant role in the development of breast, prostate, pancreatic and colon cancer. Prolonged lifetime exposure to estrogen is associated with several kinds of DNA damage. Oxidative stress and estrogen receptor-associated proliferative changes are suggested to play important roles in estrogen-induced breast carcinogenesis. BRCA1, a tumor suppressor against hormone responsive cancers such as breast and prostate cancer, plays a significant role in inhibiting ROS and estrogen mediated DNA damage; thereby regulate the redox homeostasis of the cells. Several transcription factors and tumor suppressors are involved during stress response such as Nrf2, NFκB and BRCA1. A promising strategy for targeting redox status of the cells is to use readily available natural substances from vegetables, fruits, herbs and spices. Many of the phytochemicals have already been identified to have chemopreventive potential, capable of intervening in carcinogenesis.
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