Cancer metastasis is a multistep process in which a cancer cell spreads from the site of the primary lesion, passes through the circulatory system, and establishes a secondary tumor at a new nonadjacent organ or part. Inhibition of cancer progression by dietary phytochemicals (DPs) offers significant promise for reducing the incidence and mortality of cancer. Consumption of DPs in the diet has been linked to a decrease in the rate of metastatic cancer in a number of preclinical animal models and human epidemiological studies. DPs have been reported to modulate the numerous biological events including epigenetic events (noncoding micro-RNAs, histone modification, and DNA methylation) and multiple signaling transduction pathways (Wnt/β-catenin, Notch, Sonic hedgehog, COX-2, EGFR, MAPK-ERK, JAK-STAT, Akt/PI3K/mTOR, NF-κB, AP-1, etc.), which can play a key role in regulation of metastasis cascade. Extensive studies have also been performed to determine the molecular mechanisms underlying antimetastatic activity of DPs, with results indicating that these DPs have significant inhibitory activity at nearly every step of the metastatic cascade. DPs have anticancer effects by inducing apoptosis and by inhibiting cell growth, migration, invasion, and angiogenesis. Growing evidence has also shown that these natural agents potentiate the efficacy of chemotherapy and radiotherapy through the regulation of multiple signaling pathways. In this review, we discuss the variety of molecular mechanisms by which DPs regulate metastatic cascade and highlight the potentials of these DPs as promising therapeutic inhibitors of cancer.

译文

癌症转移是一个多步骤的过程,其中癌细胞从原发病变部位扩散,通过循环系统,并在新的非相邻器官或部位建立继发性肿瘤。通过饮食植物化学物质 (DPs) 抑制癌症进展为降低癌症的发病率和死亡率提供了重要的希望。在许多临床前动物模型和人类流行病学研究中,饮食中DPs的消耗与转移性癌症的发生率降低有关。据报道,DPs可以调节许多生物学事件,包括表观遗传事件 (非编码微rna,组蛋白修饰和DNA甲基化) 和多种信号转导途径 (Wnt/β-catenin,Notch,Sonic hedgehog,COX-2,EGFR,MAPK-ERK,JAK-STAT,akt/PI3K/mTOR、NF-κ b、AP-1等),可在转移级联调控中起关键作用。还进行了广泛的研究以确定DPs抗转移活性的分子机制,结果表明这些DPs在转移级联的几乎每个步骤中都具有显着的抑制活性。DPs通过诱导细胞凋亡并抑制细胞生长,迁移,侵袭和血管生成而具有抗癌作用。越来越多的证据表明,这些天然药物通过调节多种信号通路来增强化疗和放疗的功效。在这篇综述中,我们讨论了DPs调节转移性级联反应的多种分子机制,并强调了这些DPs作为有前途的癌症治疗抑制剂的潜力。

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