Jana Neuwirthová, Břetislav Gál, Pavel Smilek, Pavla Urbánková
Klin Onkol. 2018 Spring;31(3):184-190. doi: 10.14735/amko2018184.
Naturally occurring bioactive compounds are promising candidates to prevent and treat cancer. Quercetin is a well-known plant flavonoid that is reported to have anticancer actions in vitro and in vivo. This review focuses on the molecular mechanisms underlying the chemopreventive effect of quercetin and its therapeutic potential in oncology. Quercetin elicits biphasic, hormetic, dose-dependent effects. It acts as an antioxidant and thus elicits chemopreventive effects at low concentrations, but functions as a pro-oxidant and may therefore elicit chemotherapeutic effects at high concentrations. Quercetin has multiple intracellular molecular targets with the potential to reverse treatment resistance and affect pleiotropic signaling processes that are altered in cancer cells. Studies suggest that quercetin binds to several receptors that play important roles in carcinogenesis, regulates expression of various genes, induces epigenetic changes, and interferes with enzymes that metabolize chemical carcinogens. In addition, it also elicits anti-inflammatory and antiviral effects. The ability of quercetin to induce apoptosis of cancer cells without affecting non-cancer cells has been documented using various cell lines. Quercetin also has antiangiogenic and antimetastatic properties. When used in combination with chemotherapy and radiotherapy, quercetin can act as a sensitizer and protect non-cancer cells from the side effects of currently used cancer therapies. The safety and potential usefulness of quercetin for the prevention and treatment of cancer have been documented in both animal experiments and a phase I clinical trial. Current studies are focused on nano-formulations to overcome the low bioavailability of natural quercetin, which limits its clinical use as an antitumor agent. Key words: quercetin - flavonoid - chemoprevention - oxidative stress - apoptosis - antitumor agent - cancer therapy - cancer The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 22. 1. 2018 Accepted: 16. 4. 2018.
天然存在的生物活性化合物是预防和治疗癌症的有前途的候选物。槲皮素是一种著名的植物黄酮类化合物,据报道在体外和体内均具有抗癌作用。本综述重点关注槲皮素化学预防作用的分子机制及其在肿瘤学中的治疗潜力。槲皮素会引发双相、 hormetic 、剂量依赖性效应。它作为抗氧化剂,因此在低浓度时引发化学预防作用,但在高浓度时作为促氧化剂,可能因此引发化疗作用。槲皮素有多个细胞内分子靶点,有可能逆转治疗耐药性并影响癌细胞中改变的多效性信号传导过程。研究表明,槲皮素与几种在致癌过程中起重要作用的受体结合,调节各种基因的表达,诱导表观遗传变化,并干扰代谢化学致癌物的酶。此外,它还具有抗炎和抗病毒作用。使用各种细胞系已证明槲皮素能够诱导癌细胞凋亡而不影响非癌细胞。槲皮素还具有抗血管生成和抗转移特性。当与化疗和放疗联合使用时,槲皮素可以作为增敏剂,保护非癌细胞免受目前使用的癌症治疗的副作用。槲皮素在预防和治疗癌症方面的安全性和潜在用途已在动物实验和 I 期临床试验中得到证明。目前的研究集中在纳米制剂上,以克服天然槲皮素生物利用度低的问题,这限制了其作为抗肿瘤剂的临床应用。关键词:槲皮素 - 黄酮类化合物 - 化学预防 - 氧化应激 - 细胞凋亡 - 抗肿瘤剂 - 癌症治疗 - 癌症 作者声明他们在研究中使用的药物、产品或服务方面没有潜在的利益冲突。编辑委员会声明该手稿符合 ICMJE 对生物医学论文的建议。提交日期: 2018 年 1 月 22 日 接受日期: 2018 年 4 月 16 日。