School of Applied Biosciences, Kyungpook National University, Daegu, Republic of Korea.
Pharmacol Ther. 2011 Jun;130(3):310-24. doi: 10.1016/j.pharmthera.2011.02.004. Epub 2011 Feb 26.
Multiple lines of evidences suggest that oxidative stress induced by reactive oxygen species are closely related to multi-stage carcinogenesis. Polyphenols, a group of chemicals with more than one phenol unit or building block per molecule, have been recognized for possessing many health benefits including cancer-preventive effects mainly due to their antioxidant activity. However, polyphenols can directly bind with signaling molecules involved in carcinogenesis and regulate its activity. Moreover, it is noteworthy that the binding between the polyphenol and the target protein is determined by their structural relationship, which implies that different polyphenols have different target proteins, leading to divergent chemopreventive effects. Extracellular stimuli transmit signals into a cell by activating their target signaling cascades involved in carcinogenesis. As an example, Src family kinase, a family of proto-oncogenic tyrosine kinases activated by a variety of oxidative stress and proinflammatory agents, is known to regulate cell proliferation, differentiation, survival and angiogenesis. Src family kinase subsequently activates downstream signal cascades including mitogen-activated protein kinase, phosphoinositol-3-kinase, and nuclear factor-kappaB, thereby inducing cell proliferation and causing cancer. Recent studies demonstrate that polyphenols can directly target signaling cascades involved in inflammation and the development of cancer. Inhibition of the kinases by polyphenols contributes to the attenuation of carcinogenesis. Therefore, the development of polyphenols as direct inhibitors against target proteins is regarded as a rational approach for chemoprevention. This review describes and discusses recent results about the direct interactions of polyphenols and protein kinases in cancer chemoprevention.
有多项证据表明，活性氧引起的氧化应激与多阶段致癌密切相关。多酚是一类化学物质，每个分子中含有一个以上的酚单元或结构单元，由于具有抗氧化活性，已被认为具有许多健康益处，包括预防癌症的作用。然而，多酚可以直接与参与致癌作用的信号分子结合，并调节其活性。此外，值得注意的是，多酚与靶蛋白的结合取决于它们的结构关系，这意味着不同的多酚具有不同的靶蛋白，导致不同的化学预防效果。细胞外刺激通过激活参与致癌作用的靶信号级联来将信号传入细胞。例如，Src 家族激酶是一组原癌性酪氨酸激酶，可被多种氧化应激和促炎剂激活，已知可调节细胞增殖、分化、存活和血管生成。Src 家族激酶随后激活下游信号级联，包括丝裂原激活蛋白激酶、磷酸肌醇 3-激酶和核因子-κB，从而诱导细胞增殖并导致癌症。最近的研究表明，多酚可以直接针对参与炎症和癌症发展的信号级联。多酚对激酶的抑制作用有助于减弱致癌作用。因此，将多酚开发为针对靶蛋白的直接抑制剂被认为是化学预防的一种合理方法。本文综述了多酚与蛋白激酶在癌症化学预防中的直接相互作用的最新研究结果，并进行了讨论。
