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槲皮素和绿茶在人白血病 HL60 细胞异种移植中的抗肿瘤活性。

Antitumor activities of Quercetin and Green Tea in xenografts of human leukemia HL60 cells.

机构信息

Hematology and Transfusion Medicine Center-University of Campinas/Hemocentro-UNICAMP, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.

Onco-Hematological Child Research Center, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, São Paulo, Brazil.

出版信息

Sci Rep. 2018 Feb 22;8(1):3459. doi: 10.1038/s41598-018-21516-5.

Abstract

Quercetin is one of the most abundant flavonoids, present in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Green tea is a widely consumed beverage, known for a potential source of free radical scavenging and anti-cancer activities. Herein, we investigate the in vivo antitumor efficacy of quercetin and green tea in human leukemia. Human tumors were xenografted into NOD/SCID mice. Quercetin and green tea reduced tumor growth in HL-60 xenografts accompanied by decreased expression of anti-apoptotic proteins, BCL-2, BCL-XL and MCL-1 and increased expression of BAX, a pro-apoptotic protein. Moreover, caspase-3 was activated to a greater extent after quercetin and green tea treatment. Quercetin and green tea also mediated G1 phase cell cycle arrest in HL-60 xenografts. Treatment with quercetin and green tea induced conversion of LC3-I to LC3-II as well as activation of autophagy proteins, suggesting that quercetin and green tea initiate the autophagic progression. We have provided evidence that quercetin and green tea induces signaling at the level of apoptosis, cell cycle and autophagy which converge to antigrowth effects in HL-60 xenograft mice suggesting that these compounds may be a compelling ally in cancer treatment.

摘要

槲皮素是一种最丰富的类黄酮之一,存在于水果和蔬菜中,已被证明具有多种特性,能够减少癌细胞的生长。绿茶是一种广泛消费的饮料,以自由基清除和抗癌活性的潜在来源而闻名。在此,我们研究了槲皮素和绿茶在人类白血病中的体内抗肿瘤功效。人肿瘤被异种移植到 NOD/SCID 小鼠中。槲皮素和绿茶减少了 HL-60 异种移植物的肿瘤生长,同时降低了抗凋亡蛋白 BCL-2、BCL-XL 和 MCL-1 的表达,增加了促凋亡蛋白 BAX 的表达。此外, caspase-3 在槲皮素和绿茶处理后被更有效地激活。槲皮素和绿茶还介导了 HL-60 异种移植物中的 G1 期细胞周期停滞。用槲皮素和绿茶处理诱导 LC3-I 向 LC3-II 的转化以及自噬蛋白的激活,表明槲皮素和绿茶启动了自噬进程。我们已经提供了证据,表明槲皮素和绿茶在凋亡、细胞周期和自噬水平诱导信号转导,这些信号转导在 HL-60 异种移植小鼠中 convergeto 抗肿瘤作用,表明这些化合物可能是癌症治疗中的一个强有力的盟友。

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