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苍耳草的苍耳亭诱导 CT26WT 结肠癌细胞有丝分裂停滞和细胞凋亡。

Xanthium strumarium´s xanthatins induces mitotic arrest and apoptosis in CT26WT colon carcinoma cells.

机构信息

Departamento de Toxicología Genética y antitumorales, Centro de Investigación y Desarrollo de Medicamentos (CIDEM), Avenida 26, No. 1605 e/ Puentes Grandes y Boyeros, La Habana, Cuba.

Departamento de Biología Vegetal, Laboratorio de Toxicología Genética, Facultad de Biología, Universidad de la Habana, Calle 25, No. 455, e/ I y J, Vedado, La Habana, Cuba.

出版信息

Phytomedicine. 2019 Apr;57:236-244. doi: 10.1016/j.phymed.2018.12.019. Epub 2018 Dec 17.

DOI:10.1016/j.phymed.2018.12.019
PMID:30797985
Abstract

BACKGROUND

Colorectal cancer is one of the most common malignancies worldwide and is associated with high mortality rates. We previously reported that Xanthium strumarium L. induces mitotic arrest in proliferating cells, a process mediated by xanthatins.

HYPOTHESIS/AIM: The aim of this work is to study if xanthatins, isolated from X. strumarium total extract, affect the proliferative capacity of CT26WT colon cancer cells and, in consequence, if tumor growth and proliferation of (lung) metastatic sites can also be arrested in vivo.

STUDY DESIGN

This study consisted of both in vitro and in vivo experiments involving the CT26WT cell line and a subcutaneous mouse model of colon cancer. In vitro cell cycle progression, in vivo tumoral growth and anti-metastatic activity were analyzed to investigate whether xanthatins of X. strumarium induce mitotic arrest in proliferating colorectal carcinoma.

RESULTS

Our in vitro results show that X. strumarium, mediated by xanthatins, induces G/M arrest and impair anaphase entrance. This leads to a significant induction of apoptotic and necrotic in CT26WT cells, demonstrating their significant anti-proliferative activity through interfering with the mitotic apparatus. Furthermore, our in vivoresults reveal that X. strumarium inhibits both tumor growth and metastasis progression.

CONCLUSION

X. strumarium antitumor activities are mainly mediated by xanthatins through inhibition of tumor growth and metastasis, inducing mitotic arrest and apoptosis in colon carcinoma cells. These findings further confirm the therapeutic potential of X. strumarium in colorectal cancer.

摘要

背景

结直肠癌是世界上最常见的恶性肿瘤之一,死亡率很高。我们之前的研究报告表明,苍耳通过苍耳亭诱导增殖细胞有丝分裂阻滞,这一过程由苍耳亭介导。

假说/目的:本工作的目的是研究苍耳总提物中分离的苍耳亭是否影响 CT26WT 结肠癌细胞的增殖能力,以及肿瘤生长和(肺部)转移部位的增殖是否也可以在体内被阻滞。

研究设计

本研究包括 CT26WT 细胞系和结直肠癌皮下小鼠模型的体内外实验。分析体外细胞周期进展、体内肿瘤生长和抗转移活性,以研究苍耳是否通过苍耳亭诱导增殖性结直肠癌细胞有丝分裂阻滞。

结果

我们的体外结果表明,苍耳通过苍耳亭诱导 G2/M 期阻滞并损害后期进入,导致 CT26WT 细胞中凋亡和坏死的显著诱导,表明其通过干扰有丝分裂装置具有显著的抗增殖活性。此外,我们的体内结果表明,苍耳抑制肿瘤生长和转移进展。

结论

苍耳的抗肿瘤活性主要通过苍耳亭抑制肿瘤生长和转移来介导,诱导结肠癌细胞有丝分裂阻滞和凋亡。这些发现进一步证实了苍耳在结直肠癌中的治疗潜力。

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