Rutacridone Downregulates PI3K/AKT Signalling Pathway and promotes miR-145 Expression in Cell Cycle Arrest and Apoptosis of Gastric Cancer Cells

被引：0
作者：
Li, Hong [1 ]
Zhang, Yinbin [2 ]
Liu, Na [1 ]
Wang, Jinhai [1 ]
机构：
[1] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Gastroenterol, Xian 710004, Shaanxi, Peoples R China
[2] Xi An Jiao Tong Univ, Affiliated Hosp 2, Dept Oncol, Xian 710004, Shaanxi, Peoples R China
来源：
LATIN AMERICAN JOURNAL OF PHARMACY | 2021年 / 40卷 / 10期
关键词：
apoptosis; cell cycle arrest; miR-145; PI3K/AKT; rutacridone; PROLIFERATION;
D O I：
暂无
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Ruta graveolens Linn. has been used traditionally as antiseptic, abortificient, anti-rheumatic, anti-inflammatory, anti-androgenic, and anti-hyperglycemic agent. The present study investigated the effect of rutacridone, a compound isolated from R. graveolens on gastric cancer cells and explored the underlying mechanism. The study demonstrated that treatment of AGS and NCI-N87 cancer cells with rutacridone significantly (p < 0.05) decreased cell viability but couldn't affect normal, GES1 cell viability. Rutacridone treatment of AGS cells significantly (p < 0.05) increased apoptosis induction compared to the control cells. Moreover, treatment of AGS cells with rutacridone significantly (p < 0.05) increased percentage of cells in the G1-phase of cell cycle. Additionally, treatment of AGS cells with 0.75 to 24 mu M rutacridone caused a concentration-dependent decrease in invasion potential. It caused a marked increase in miR145 expression in AGS cells and reduced cMyc, PI3K, pAKT, MMP2 and MMP9 expression compared to the control cells. In summary, rutacridone inhibits gastric cancer cell viability in vitro by induction of cell apoptosis and arrest of cell cycle. Moreover, rutacridone promoted miR145 expression and down-regulation of PI3K/AKT signaling pathway in AGS cells. Therefore, rutacridone can be used as a potential therapeutic candidate for treatment of gastric cancer.
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页码：2287 / 2292
页数：6
相关论文
共 18 条
[1]   The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches [J].
De Luca, Antonella ;
Maiello, Monica R. ;
D'Alessio, Amelia ;
Pergameno, Maria ;
Normanno, Nicola .
EXPERT OPINION ON THERAPEUTIC TARGETS, 2012, 16 :S17-S27
[2]   RETRACTED: The molecular mechanism of microRNA-145 to suppress invasion-metastasis cascade in gastric cancer (Retracted Article) [J].
Gao, P. ;
Xing, A-Y ;
Zhou, G-Y ;
Zhang, T-G ;
Zhang, J-P ;
Gao, C. ;
Li, H. ;
Shi, D-B .
ONCOGENE, 2013, 32 (04) :491-501
[3]   Metastatic gastric cancer treatment: Second line and beyond [J].
Ghosn, Marwan ;
Tabchi, Samer ;
Kourie, Hampig Raphael ;
Tehfe, Mustapha .
WORLD JOURNAL OF GASTROENTEROLOGY, 2016, 22 (11) :3069-3077
[4]  
Guimarães Raphael Mendonça, 2012, Arq. Gastroenterol., V49, P184, DOI 10.1590/S0004-28032012000300003
[5]   An overview of microRNAs [J].
Hammond, Scott M. .
ADVANCED DRUG DELIVERY REVIEWS, 2015, 87 :3-14
[6]   MEDIATION OF C-MYC-INDUCED APOPTOSIS BY P53 [J].
HERMEKING, H ;
EICK, D .
SCIENCE, 1994, 265 (5181) :2091-2093
[7]   miR-143 and miR-145 inhibit gastric cancer cell migration and metastasis by suppressing MYO6 [J].
Lei, Chao ;
Du, Feng ;
Sun, Lina ;
Li, Ting ;
Li, Tingyu ;
Min, Yali ;
Nie, Aiying ;
Wang, Xin ;
Geng, Lei ;
Lu, Yuanyuan ;
Zhao, Xiaodi ;
Shi, Yongquan ;
Fan, Daiming .
CELL DEATH & DISEASE, 2017, 8 :e3101-e3101
[8]   c-Myc augments gamma irradiation-induced apoptosis by suppressing Bcl-XL [J].
Maclean, KH ;
Keller, UB ;
Rodriguez-Galindo, C ;
Nilsson, JA ;
Cleveland, JL .
MOLECULAR AND CELLULAR BIOLOGY, 2003, 23 (20) :7256-7270
[9]   How microRNAs control cell division, differentiation and death [J].
Miska, EA .
CURRENT OPINION IN GENETICS & DEVELOPMENT, 2005, 15 (05) :563-568
[10]  
Nadkarni K M., 2009, Indian Materia Medica, V1st
12