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木犀草素通过 p53 依赖性途径诱导 HCT116 结肠癌细胞凋亡和自噬。

Luteolin Induces Apoptosis and Autophagy in HCT116 Colon Cancer Cells via p53-Dependent Pathway.

机构信息

Department of Food and Nutrition, Seoul National University, Seoul, Korea.

Department of Human Nutrition and Food Science, Chungwoon University, Hongseong, Chungnam, Korea.

出版信息

Nutr Cancer. 2022;74(2):677-686. doi: 10.1080/01635581.2021.1903947. Epub 2021 Mar 24.

Abstract

Although a dietary phytochemical luteolin has been shown to regulate various anticancer mechanisms, a role of luteolin in autophagy regulation is mostly unidentified. Here, we investigated whether luteolin exhibits its anticancer effects by induction of apoptosis and autophagy in a p53-dependent manner in colon cancer cells. Cell viability was determined using trypan blue exclusion test. The expressions of proteins and mRNAs were measured by immunoblotting and reverse transcription polymerase chain reaction, respectively. Luteolin at 10 - 20 μM induced cytotoxicity in p53 wild-type HCT116 colon cancer cells but not in p53 mutant HT-29 cells and normal colon cells. Luteolin exhibited its anticancer effect by increasing p53 phosphorylation and p53 target gene expression, leading to apoptosis and cell cycle arrest in HCT116 cells. We identified that luteolin can induce autophagy in p53 wild-type cells but not in p53 mutant cells, suggesting that luteolin-induced autophagy is p53-dependent; however, chloroquine-mediated inhibition of autophagy did not alter cytotoxicity and apoptosis of cells treated with luteolin. In conclusion, the present data showed that luteolin inhibits the growth of HCT116 colon cancer cells through p53-dependent regulation of apoptosis and cell cycle arrest regardless of the induction of autophagy.

摘要

尽管膳食植物化学物木樨草素已被证明可调节多种抗癌机制,但木樨草素在自噬调节中的作用大多尚未确定。在这里,我们研究了木樨草素是否通过诱导 p53 依赖性凋亡和自噬来发挥其在结肠癌细胞中的抗癌作用。使用台盼蓝排除试验测定细胞活力。通过免疫印迹和逆转录聚合酶链反应分别测量蛋白质和 mRNA 的表达。10-20 μM 的木樨草素在 p53 野生型 HCT116 结肠癌细胞中诱导细胞毒性,但在 p53 突变型 HT-29 细胞和正常结肠细胞中没有诱导。木樨草素通过增加 p53 磷酸化和 p53 靶基因表达,导致 HCT116 细胞凋亡和细胞周期停滞,从而发挥抗癌作用。我们发现木樨草素可以在 p53 野生型细胞中诱导自噬,但不能在 p53 突变型细胞中诱导,表明木樨草素诱导的自噬依赖于 p53;然而,氯喹介导的自噬抑制并没有改变用木樨草素处理的细胞的细胞毒性和凋亡。总之,本研究数据表明,木樨草素通过 p53 依赖性调节凋亡和细胞周期阻滞抑制 HCT116 结肠癌细胞的生长,而与自噬的诱导无关。

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