Osthole impairs mitochondrial metabolism and the autophagic flux in colorectal cancer

细胞凋亡 结直肠癌 自噬 癌症研究 化学 活力测定 活性氧 偶氮甲烷 程序性细胞死亡 线粒体 药理学 细胞生物学 生物 癌症 内科学 生物化学 医学
作者
Jisoo Song,Jiyeon Ham,Wonhyoung Park,Gwonhwa Song,Whasun Lim
出处
期刊:Phytomedicine [Elsevier]
卷期号:125: 155383-155383 被引量:4
标识
DOI:10.1016/j.phymed.2024.155383
摘要

Osthole is active constituent of Cnidium monnieri (L.) Cuss. with various physiological functions including anti-inflammation and anti-lipedemic effects. However, the regulatory activity of osthole in colorectal cancer development, focusing on mitochondrial metabolism, is not well known. We hypothesized that osthole may suppress progression of colorectal cancer and aimed to determine the underlying mitochondrial metabolism and the autophagic flux. In this study, we elucidated the mechanism of action of osthole in colorectal cancer using an in vivo azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model and an in vitro cell culture system. AOM/DSS mouse model was established and analyzed the effects of osthole on survival rate, diseases activity index, number of tumor and histopathology. Then, cell based assays including viability, cell cycle, reactive oxygen species (ROS), apoptosis, calcium efflux, and mitochondrial function were analyzed. Moreover, osthole-mediated signaling was demonstrated by western blot analyses. Osthole effectively suppressed the growth of colorectal tumors and alleviated AOM/DSS-induced intestinal injury. Osthole restored the function of goblet cells and impaired the expression of Claudin1 and Axin1 impaired by AOM/DSS. In addition, osthole specifically showed cytotoxicity in colorectal carcinoma cells, but not in normal colon cells. Osthole decreased the ASC/caspase-1/IL-1β inflammasome pathway and induced mitochondrial dysfunction in redox homeostasis, calcium homeostasis. Furthermore, osthole inhibited both oxidative phosphorylation (OXPHOS) and glycolysis, leading to the suppression of ATP production. Moreover, via combination treatment with chloroquine (CQ), we demonstrated that osthole impaired autophagic flux, leading to apoptosis of HCT116 and HT29 cells. Finally, we elucidated that the functional role of tiRNAHisGTG regulated by osthole directly affects the cellular fate of colon cancer cells. These results suggest that osthole has the potential to manage progression of colorectal cancer by regulating autophagy- and mitochondria-mediated signal transduction.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
符聪完成签到 ,获得积分10
刚刚
轻松的采枫完成签到,获得积分10
刚刚
acffo完成签到 ,获得积分10
刚刚
3秒前
脾气暴躁的小兔完成签到,获得积分10
8秒前
东方一斩发布了新的文献求助10
8秒前
9秒前
10秒前
科目三应助郝宝真采纳,获得10
10秒前
东方一斩完成签到,获得积分10
13秒前
念工人发布了新的文献求助10
15秒前
星河鱼完成签到,获得积分10
17秒前
dong完成签到,获得积分10
19秒前
平淡雪枫完成签到 ,获得积分10
21秒前
折木完成签到,获得积分10
21秒前
方芳芳发布了新的文献求助10
22秒前
科研通AI2S应助dong采纳,获得10
23秒前
骆子军完成签到 ,获得积分10
25秒前
科目三应助guchenniub采纳,获得10
25秒前
在水一方应助念工人采纳,获得10
25秒前
27秒前
hui发布了新的文献求助10
29秒前
卜念发布了新的文献求助10
29秒前
liu完成签到 ,获得积分10
29秒前
30秒前
xff完成签到,获得积分20
31秒前
爆米花应助无剑采纳,获得10
33秒前
guchenniub发布了新的文献求助10
36秒前
xff发布了新的文献求助30
36秒前
tyanna完成签到,获得积分10
36秒前
小耗子完成签到,获得积分10
38秒前
42秒前
iNk应助guchenniub采纳,获得10
43秒前
大卫在分享应助guchenniub采纳,获得10
43秒前
陀思妥耶夫斯基完成签到 ,获得积分10
48秒前
iWatchTheMoon应助危机的寄文采纳,获得10
48秒前
49秒前
大方的云朵完成签到,获得积分10
50秒前
NexusExplorer应助PGR采纳,获得20
51秒前
52秒前
高分求助中
Evolution 10000
ISSN 2159-8274 EISSN 2159-8290 1000
Becoming: An Introduction to Jung's Concept of Individuation 600
Ore genesis in the Zambian Copperbelt with particular reference to the northern sector of the Chambishi basin 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3162987
求助须知:如何正确求助?哪些是违规求助? 2813990
关于积分的说明 7902734
捐赠科研通 2473613
什么是DOI,文献DOI怎么找? 1316952
科研通“疑难数据库(出版商)”最低求助积分说明 631560
版权声明 602187