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海藻中具有抗白血病活性的生物活性化合物:类胡萝卜素和岩藻黄质的综述。

Bioactive Compounds from Seaweed with Anti-Leukemic Activity: A Mini-Review on Carotenoids and Phlorotannins.

机构信息

Team of Histomorphology, Physiopathology and Applied Toxicology, CIIMAR/CIMAR - Interdisciplinary Center for Marine and Environmental Research, U.Porto - University of Porto, Avenida General Norton de Matos s/n, 4450-208 Matosinhos, Portugal.

Laboratory of Histology and Embryology, Department of Microscopy, ICBAS - Institute of Biomedical Sciences Abel Salazar, U.Porto - University of Porto, Rua de Jorge Viterbo Ferreira, no 228, 4050-313 Porto, Portugal.

出版信息

Mini Rev Med Chem. 2020;20(1):39-53. doi: 10.2174/1389557519666190311095655.

Abstract

Chronic Myeloid Leukemia (CML) represents 15-20% of all new cases of leukemia and is characterized by an uncontrolled proliferation of abnormal myeloid cells. Currently, the first-line of treatment involves Tyrosine Kinase Inhibitors (TKIs), which specifically inhibits the activity of the fusion protein BCR-ABL. However, resistance, mainly due to mutations, can occur. In the attempt to find more effective and less toxic therapies, several approaches are taken into consideration such as research of new anti-leukemic drugs and "combination chemotherapy" where different drugs that act by different mechanisms are used. Here, we reviewed the molecular mechanisms of CML, the main mechanisms of drug resistance and current strategies to enhance the therapeutic effect of TKIs in CML. Despite major advances in CML treatment, new, more potent anticancer drugs and with fewer side effects are needed. Marine organisms, and particularly seaweed, have a high diversity of bioactive compounds with some of them having anticancer activity in several in vitro and in vivo models. The state-of-art suggests that their use during cancer treatment may improve the outcome. We reviewed here the yet few data supporting anti-leukemic activity of some carotenoids and phlorotannins in some leukemia models. Also, strategies to overcome drug resistance are discussed, particularly the combination of conventional drugs with natural compounds.

摘要

慢性髓性白血病 (CML) 占所有新发白血病的 15-20%,其特征是异常髓样细胞的不受控制增殖。目前,一线治疗涉及酪氨酸激酶抑制剂 (TKI),其特异性抑制融合蛋白 BCR-ABL 的活性。然而,主要由于突变,可能会发生耐药性。为了寻找更有效和毒性更小的治疗方法,考虑了几种方法,例如研究新的抗白血病药物和“联合化疗”,其中使用通过不同机制起作用的不同药物。在这里,我们综述了 CML 的分子机制、主要耐药机制以及目前增强 CML 中 TKI 治疗效果的策略。尽管 CML 治疗取得了重大进展,但仍需要新的、更有效的抗癌药物,且副作用更少。海洋生物,特别是海藻,具有高度多样化的生物活性化合物,其中一些在几种体外和体内模型中具有抗癌活性。最先进的技术表明,在癌症治疗期间使用它们可能会改善结果。在这里,我们回顾了一些支持某些类胡萝卜素和岩藻黄质在某些白血病模型中具有抗白血病活性的少数数据。此外,还讨论了克服耐药性的策略,特别是将传统药物与天然化合物联合使用。

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