A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells.
A Comprehensive Analysis and Anti-Cancer Activities of Quercetin in ROS-Mediated Cancer and Cancer Stem Cells.
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DOI：
10.3390/ijms231911746
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发表时间：
2022-10-04
影响因子：
5.6
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中科院分区：
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活性氧（ROS）通过引起基因突变、激活癌基因和增加氧化应激而诱导癌发生，所有这些都影响细胞增殖、存活和凋亡。与正常细胞相比，癌细胞具有更高水平的ROS，并且它们负责维持癌症表型;因此，癌细胞中的这种独特特征可以用于靶向治疗。槲皮素（Quercetin，QC）是一种植物源性生物活性物质，具有清除活性氧的作用，近年来被发现对多种实体瘤具有抗肿瘤作用。适应性应激反应可以由持续的ROS应激诱导，允许癌细胞在高水平的ROS下存活，同时保持细胞活力。然而，大量的活性氧使癌细胞对槲皮素（最有效的膳食黄酮之一）极其敏感。由于恶性细胞和正常细胞之间的分子和代谢差异，靶向ROS代谢可能有助于克服耐药性并实现治疗选择性，同时对正常细胞几乎没有影响。槲皮素强大的生物活性和调节作用促使人们对这种化学物质进行了广泛的研究，已经确定了许多可能共同预防癌症的途径，同时，QC有大量证据可用作癌症干细胞的治疗剂。目前的研究已经广泛地证明了槲皮素的功能机制关系以及它如何调节ROS的产生以杀死癌症和癌症干细胞。在此，我们揭示了ROS在正常细胞和癌细胞中的调节和产生具有一定的信号传导机制。我们阐述了槲皮素在肿瘤细胞死亡中的特异性分子机制，包括MAPK/ERK 1/2、p53、JAK/STAT和TRAIL、AMPKα1/ASK 1/p38、MAPK/PI 3 K/AKT/mTOR轴、HMGB 1和NF-κB、Nrf 2诱导的信号通路和某些细胞周期阻滞，以及它们如何调节特异性肿瘤信号通路作为长期探索的肿瘤治疗剂。
Reactive oxygen species (ROS) induce carcinogenesis by causing genetic mutations, activating oncogenes, and increasing oxidative stress, all of which affect cell proliferation, survival, and apoptosis. When compared to normal cells, cancer cells have higher levels of ROS, and they are responsible for the maintenance of the cancer phenotype; this unique feature in cancer cells may, therefore, be exploited for targeted therapy. Quercetin (QC), a plant-derived bioflavonoid, is known for its ROS scavenging properties and was recently discovered to have various antitumor properties in a variety of solid tumors. Adaptive stress responses may be induced by persistent ROS stress, allowing cancer cells to survive with high levels of ROS while maintaining cellular viability. However, large amounts of ROS make cancer cells extremely susceptible to quercetin, one of the most available dietary flavonoids. Because of the molecular and metabolic distinctions between malignant and normal cells, targeting ROS metabolism might help overcome medication resistance and achieve therapeutic selectivity while having little or no effect on normal cells. The powerful bioactivity and modulatory role of quercetin has prompted extensive research into the chemical, which has identified a number of pathways that potentially work together to prevent cancer, alongside, QC has a great number of evidences to use as a therapeutic agent in cancer stem cells. This current study has broadly demonstrated the function-mechanistic relationship of quercetin and how it regulates ROS generation to kill cancer and cancer stem cells. Here, we have revealed the regulation and production of ROS in normal cells and cancer cells with a certain signaling mechanism. We demonstrated the specific molecular mechanisms of quercetin including MAPK/ERK1/2, p53, JAK/STAT and TRAIL, AMPKα1/ASK1/p38, RAGE/PI3K/AKT/mTOR axis, HMGB1 and NF-κB, Nrf2-induced signaling pathways and certain cell cycle arrest in cancer cell death, and how they regulate the specific cancer signaling pathways as long-searched cancer therapeutics.
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影响因子：
4.7
作者：
通讯作者：
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影响因子：
4.7
作者：
Chen, Wenshu;Wang, Xia;Lin, Yong
通讯作者：
Lin, Yong
影响因子：
2.8
作者：
Chien, Su-Yu;Wu, Yao-Chung;Chen, Dar-Ren
通讯作者：
Chen, Dar-Ren
影响因子：
2.9
作者：
Chen W;Druhan LJ;Chen CA;Hemann C;Chen YR;Berka V;Tsai AL;Zweier JL
通讯作者：
Zweier JL
影响因子：
0.7
作者：
Chen X
通讯作者：
Chen X