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Vitamin K1 Exerts Antiproliferative Effects and Induces Apoptosis in Three Differently Graded Human Colon Cancer Cell Lines

机译:维生素K1在三种不同等级的人类结肠癌细胞系中发挥抗增殖作用并诱导其凋亡

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摘要

Vitamin K1 has been demonstrated as having anticancer potentiality mainly in liver cancer cells. Beyond the reported mechanisms of cancer inhibition (cell cycle arrest and induction of apoptosis), a possible control by vitamin K1 on molecules affecting cell growth could be hypothesized. In the literature, few (if any) data are available on its antitumor effects on colon cancer cells. Therefore, the aims of the study were to investigate in three differently graded human colon cancer cell lines (Caco-2, HT-29, and SW480) the effects of increasing concentrations of vitamin K1 (from 10 μM to 200 μM) administered up to 72 h on (1) cell proliferation, (2) apoptosis with the possible involvement of the MAPK pathway, and (3) polyamine biosynthesis. Vitamin K1 treatment caused a significant antiproliferative effect and induced apoptosis in all the cell lines, with the involvement of the MAPK pathway. A concomitant and significant decrease in the polyamine biosynthesis occurred. This is the first study demonstrating a significant polyamine decrease in addition to the antiproliferative and proapoptotic effects following vitamin K1 administration to colon cancer cell lines. Therapeutically, combinations of vitamin K1 with polyamine inhibitors and/or analogues may represent a suitable option for chemoprevention and/or treatment in future strategies for colorectal cancer management.
机译:维生素K1已被证明主要在肝癌细胞中具有抗癌潜力。除了已报道的抑制癌症的机制(细胞周期停滞和诱导凋亡),还可以推测维生素K1对影响细胞生长的分子的可能控制作用。在文献中,几乎没有(如果有的话)关于其对结肠癌细胞的抗肿瘤作用的数据。因此,本研究的目的是研究在三种不同等级的人类结肠癌细胞系(Caco-2,HT-29和SW480)中增加维生素K1的浓度(从10μm至200μm)的影响。 72小时:(1)细胞增殖,(2)可能参与MAPK途径的凋亡和(3)多胺生物合成。维生素K1的治疗在MAPK途径的参与下,在所有细胞系中均具有显着的抗增殖作用并诱导了细胞凋亡。随之而来的是聚胺生物合成的显着减少。这是第一项研究,表明在向结肠癌细胞系施用维生素K1后,多胺显着减少了除抗增殖和促凋亡作用外的多胺含量。在治疗上,维生素K1与多胺抑制剂和/或类似物的组合可能代表未来大肠癌治疗策略中化学预防和/或治疗的合适选择。

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