Curcumin inhibits the growth of liver cancer stem cells through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway

被引:44
作者
Wang, Ji [1 ]
Wang, Chunying [1 ]
Bu, Gaofeng [1 ]
机构
[1] Xuzhou Infect Dis Hosp, Dept Liver Dis, 63 Shuangyong Rd, Xuzhou 221004, Jiangsu, Peoples R China
关键词
apoptosis; curcumin; liver cancer; phosphatidylinositol; 3-kinase; protein kinase B; mammalian target of rapamycin; stem cells; EPITHELIAL-MESENCHYMAL TRANSITION; HEPATOCELLULAR-CARCINOMA CELLS; DOWN-REGULATION; TUMOR-GROWTH; APOPTOSIS; PI3K/AKT; METASTASIS; ROLES; PROLIFERATION; BISTABILITY;
D O I
10.3892/etm.2018.5805
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cancer stem cells are considered as a main cause of cancer recurrence. In the present study, the effects of curcumin on the growth of liver cancer stem cells (LCSCs) were investigated. The proliferation and apoptosis of LCSCs were assessed by MTT assays and flow cytometry. Changes in the expression of apoptosis-related proteins were identified by western blotting. The results of the study demonstrated that curcumin treatment inhibited the growth of LCSCs, induced cell apoptosis, as well as regulated the expression of apoptosis-associated proteins and the release of cytochrome c. Further experiments revealed that treatment with curcumin inhibited that the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Treatment with an activator of PI3K/AKT reversed the curcumin-induced growth inhibition of LCSCs. These results demonstrated that curcumin inhibited the growth of LCSCs through the PI3K/AKT/mTOR signaling pathway. Thus, the present study suggested that curcumin may be a potentially efficient agent in the treatment of liver cancer.
引用
收藏
页码:3650 / 3658
页数:9
相关论文
共 57 条
[1]   Curcumin ameliorates liver damage and progression of NASH in NASH-HCC mouse model possibly by modulating HMGB1-NF-κB translocation [J].
Afrin, Rejina ;
Arumugam, Somasundaram ;
Rahman, Azizur ;
Wahed, Mir Imam Ibne ;
Karuppagounder, Vengadeshprabhu ;
Harima, Meilei ;
Suzuki, Hiroshi ;
Miyashita, Shizuka ;
Suzuki, Kenji ;
Yoneyama, Hiroyuki ;
Ueno, Kazuyuki ;
Watanabe, Kenichi .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2017, 44 :174-182
[2]  
Aggarwal BB, 2003, ANTICANCER RES, V23, P363
[3]   Bistability in apoptosis: Roles of Bax, Bcl-2, and mitochondrial permeability transition pores [J].
Bagci, EZ ;
Vodovotz, Y ;
Billiar, TR ;
Ermentrout, GB ;
Bahar, I .
BIOPHYSICAL JOURNAL, 2006, 90 (05) :1546-1559
[4]  
Bhandarkar SS, 2007, ADV EXP MED BIOL, V595, P185
[5]   Effects of curcumin in pediatric epithelial liver tumors: inhibition of tumor growth and alpha-fetoprotein in vitro and in vivo involving the NFkappaB- and the beta-catenin pathways [J].
Bortel, Nicola ;
Armeanu-Ebinger, Sorin ;
Schmid, Evi ;
Kirchner, Bettina ;
Frank, Jan ;
Kocher, Alexa ;
Schiborr, Christina ;
Warmann, Steven ;
Fuchs, Joerg ;
Ellerkamp, Verena .
ONCOTARGET, 2015, 6 (38) :40680-40691
[6]   Management of hepatoceullular carcinoma [J].
Bruix, J ;
Sherman, M .
HEPATOLOGY, 2005, 42 (05) :1208-1236
[7]   Curcumin Suppresses Doxorubicin-Induced Epithelial-Mesenchymal Transition via the Inhibition of TGF-β and PI3K/AKT Signaling Pathways in Triple-Negative Breast Cancer Cells [J].
Chen, Wei-Chih ;
Lai, Ying-An ;
Lin, Ying-Chao ;
Ma, Jui-Wen ;
Huang, Li-Fen ;
Yang, Ning-Sun ;
Ho, Chi-Tang ;
Kuo, Sheng-Chu ;
Way, Tzong-Der .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2013, 61 (48) :11817-11824
[8]  
Cheng AL, 2001, ANTICANCER RES, V21, P2895
[9]  
Chiablaem K, 2014, ANTICANCER RES, V34, P1857
[10]   PI3k/Akt signalling pathway plays a crucial role in the anti-inflammatory effects of curcumin in LPS-activated microglia [J].
Cianciulli, Antonia ;
Calvello, Rosa ;
Porro, Chiara ;
Trotta, Teresa ;
Salvatore, Rosaria ;
Panaro, Maria Antonietta .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2016, 36 :282-290