Assi Mohamad
Laboratory "Movement, Sport and Health Sciences," University of Rennes II-Ecole Normale Superieur Rennes, France
Am J Physiol Regul Integr Comp Physiol. 2017 Dec 1;313(6):R646-R653. doi: 10.1152/ajpregu.00247.2017. Epub 2017 Aug 23.
The large doses of vitamins C and E and β-carotene used to reduce reactive oxygen species (ROS) production and oxidative damages in cancerous tissue have produced disappointing and contradictory results. This therapeutic conundrum was attributed to the double-faced role of ROS, notably, their ability to induce either proliferation or apoptosis of cancer cells. However, for a ROS-inhibitory approach to be effective, it must target ROS when they induce proliferation rather than apoptosis. On the basis of recent advances in redox biology, this review underlined a differential regulation of prooxidant and antioxidant system, respective to the stage of cancer. At early precancerous and neoplastic stages, antioxidant activity decreases and ROS appear to promote cancer initiation via inducing oxidative damage and base pair substitution mutations in prooncogenes and tumor suppressor genes, such as and , respectively. Whereas in late stages of cancer progression, tumor cells escape apoptosis by producing high levels of intracellular antioxidants, like NADPH and GSH, via the pentose phosphate pathway to buffer the excessive production of ROS and related intratumor oxidative injuries. Therefore, antioxidants should be prohibited in patients with advanced stages of cancer and/or undergoing anticancer therapies. Interestingly, the biochemical and biophysical properties of some polyphenols allow them to selectively recognize tumor cells. This characteristic was exploited to design and deliver nanoparticles coated with low doses of polyphenols and containing chemotherapeutic drugs into tumor-bearing animals. First results are encouraging, which may revolutionize the conventional use of antioxidants in cancer.
用于减少癌组织中活性氧（ROS）产生和氧化损伤的大剂量维生素C、维生素E和β-胡萝卜素产生了令人失望且相互矛盾的结果。这一治疗难题归因于ROS的双面作用，尤其是它们诱导癌细胞增殖或凋亡的能力。然而，要使ROS抑制方法有效，必须在ROS诱导增殖而非凋亡时对其进行靶向作用。基于氧化还原生物学的最新进展，本综述强调了促氧化剂和抗氧化剂系统在癌症不同阶段的差异调节。在癌前和肿瘤形成的早期阶段，抗氧化活性降低，ROS似乎通过分别诱导原癌基因和肿瘤抑制基因（如 和 ）中的氧化损伤和碱基对替代突变来促进癌症的起始。而在癌症进展的后期阶段，肿瘤细胞通过戊糖磷酸途径产生高水平的细胞内抗氧化剂（如NADPH和GSH）来逃避凋亡，以缓冲ROS的过量产生和相关的肿瘤内氧化损伤。因此，对于癌症晚期患者和/或正在接受抗癌治疗的患者应禁用抗氧化剂。有趣的是，一些多酚的生化和生物物理特性使其能够选择性地识别肿瘤细胞。利用这一特性设计并将包裹低剂量多酚且含有化疗药物的纳米颗粒递送至荷瘤动物体内。初步结果令人鼓舞，这可能会彻底改变抗氧化剂在癌症治疗中的传统应用。
