Di Domenico F, Foppoli C, Coccia R, Perluigi M
Department of Biochemical Sciences, Sapienza University of Rome, P.le A. Moro, 5-00185 Rome, Italy.
Biochim Biophys Acta. 2012 May;1822(5):737-47. doi: 10.1016/j.bbadis.2011.10.005. Epub 2011 Oct 12.
Cervical cancer lesions are a major threat to the health of women, representing the second most common cancer worldwide. The unanimously recognized etiological factor in the causation of cervical cancer is the infection with human papilloma virus (HPV). HPV infection, although necessary, is not per se sufficient to induce cancer. Other factors have to be involved in the progression of infected cells to the full neoplastic phenotype. Oxidative stress represents an interesting and under-explored candidate as a promoting factor in HPV-initiated carcinogenesis. Oxidative stress is known to perturb the cellular redox status thus leading to alteration of gene expression responses through the activation of several redox-sensitive transcription factors. This signaling cascade affects both cell growth and cell death. The ability of naturally occurring antioxidants to modulate cellular signal transduction pathways, through the activation/repression of multiple redox-sensitive transcription factors, has been claimed for their potential therapeutic use as chemopreventive agents. Among these compounds, polyphenols have been found to be promising agents toward cervical cancer. In addition to acting as antioxidants, polyphenols display a wide variety of biological function including induction of apoptosis, growth arrest, inhibition of DNA synthesis and modulation of signal transduction pathways. They can interfere with each stage of carcinogenesis initiation, promotion and progression to prevent cancer development. The present review discusses current knowledge of the major molecular pathways, which are involved in HPV-driven cancerogenesis, and the ability of polyphenols to modulate these pathways. By acting at specific steps of viral transformation cascade, polyphenols have been demonstrated to selectively inhibit tumor cell growth and may be a promising therapeutic tool for treatment of cervical cancer. In addition, recent results obtained in clinical trials using polyphenols are also discussed. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
宫颈癌病变对女性健康构成重大威胁，是全球第二大常见癌症。人乳头瘤病毒（HPV）感染是宫颈癌发病中公认的病因。HPV感染虽属必要条件，但本身并不足以诱发癌症。其他因素也参与了受感染细胞向完全肿瘤表型的进展过程。氧化应激作为HPV引发癌变的促进因素，是一个有趣且尚未充分探索的候选因素。已知氧化应激会扰乱细胞氧化还原状态，从而通过激活多种氧化还原敏感转录因子导致基因表达反应改变。这一信号级联反应会影响细胞生长和细胞死亡。天然抗氧化剂通过激活/抑制多种氧化还原敏感转录因子来调节细胞信号转导途径的能力，使其有望作为化学预防剂用于治疗。在这些化合物中，多酚已被发现是对宫颈癌有潜在作用的药物。除了作为抗氧化剂发挥作用外，多酚还具有多种生物学功能，包括诱导细胞凋亡、生长停滞、抑制DNA合成以及调节信号转导途径。它们可以干扰致癌过程的起始、促进和进展的各个阶段，以预防癌症发展。本综述讨论了目前关于HPV驱动癌变所涉及的主要分子途径的知识，以及多酚调节这些途径的能力。通过作用于病毒转化级联反应的特定步骤，多酚已被证明能选择性抑制肿瘤细胞生长，可能是治疗宫颈癌的一种有前景的治疗工具。此外，还讨论了使用多酚进行临床试验的最新结果。本文是名为：疾病中的抗氧化剂和抗氧化治疗的特刊的一部分。
