Biochemistry and Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi-221005, India.
Biosci Rep. 2012 Apr 1;32(2):161-70. doi: 10.1042/BSR20110043.
NF-κB (nuclear factor κB) plays a significant role in inflammation, immunity, cell proliferation, apoptosis and malignancy. ROS (reactive oxygen species) are among the most important regulating factors of NF-κB. Intracellular ROS are mainly regulated by an endogenous antioxidant defence system. Any disruption of redox balance leads to oxidative stress, which causes a number of pathological conditions including inflammation and malignancy. Increased metabolic activity in cancerous cells leads to oxidative stress, which is further enhanced due to depletion of the endogenous antioxidant defence system. However, the activation and signalling of NF-κB are reported to be inhibited by overexpression and induced activity of antioxidant enzymes. Therefore the present study focuses on the correlation between the endogenous antioxidant defence system, ROS and NF-κB activation during lymphoma growth in mice. The study highlights the anti-carcinogenic role of curcumin by modulation of NF-κB activation and oxidative stress via the endogenous antioxidant defence system. Oxidative stress was monitored by lipid peroxidation, protein carbonylation and antioxidant enzyme activity. NF-κB-mediated signalling was tested by DNA-binding activity. The results reflect that intracellular production of H2O2 in oxidative tumour micro-environment regulates NF-κB activation. Curcumin inhibits oxidative state in the liver of lymphoma-bearing mice by enhancing the transcription and activities of antioxidant enzymes, which in turn modulate activation of NF-κB, leading to a decrease in lymphoma growth. Morphological changes as well as cell proliferation and cell survival assays confirmed reduced lymphoma growth. Thus curcumin contributes to cancer prevention by disrupting the vicious cycle of constant ROS production, responsible for a high oxidative micro-environment for tumour growth.
NF-κB（核因子κB）在炎症、免疫、细胞增殖、凋亡和恶性肿瘤中发挥重要作用。ROS（活性氧）是 NF-κB 的最重要调节因子之一。细胞内 ROS 主要受内源性抗氧化防御系统调节。任何氧化还原平衡的破坏都会导致氧化应激，从而导致许多病理状况，包括炎症和恶性肿瘤。癌细胞代谢活性增加导致氧化应激，由于内源性抗氧化防御系统的消耗，氧化应激进一步增强。然而，据报道，抗氧化酶的过表达和诱导活性会抑制 NF-κB 的激活和信号转导。因此，本研究重点研究了在小鼠淋巴瘤生长过程中，内源性抗氧化防御系统、ROS 和 NF-κB 激活之间的相关性。该研究通过内源性抗氧化防御系统调节 NF-κB 激活和氧化应激，强调了姜黄素的抗癌作用。通过脂质过氧化、蛋白质羰基化和抗氧化酶活性监测氧化应激。通过 DNA 结合活性测试 NF-κB 介导的信号转导。结果反映了氧化肿瘤微环境中 H2O2 的细胞内产生调节 NF-κB 激活。姜黄素通过增强抗氧化酶的转录和活性，抑制淋巴瘤荷瘤小鼠肝脏中的氧化状态，从而调节 NF-κB 的激活，导致淋巴瘤生长减少。形态变化以及细胞增殖和细胞存活测定证实了淋巴瘤生长的减少。因此，姜黄素通过破坏导致肿瘤生长高氧化微环境的持续 ROS 产生的恶性循环，有助于癌症预防。
