Cucurbitacin B suppresses metastasis mediated by reactive oxygen species (ROS) via focal adhesion kinase (FAK) in breast cancer MDA-MB-231 cells.
10.1016/S1875-5364(18)30025-6
- Author:
Wei-Wei LUO
1
;
Wen-Wen ZHAO
1
;
Jin-Jian LU
1
;
Yi-Tao WANG
2
;
Xiu-Ping CHEN
3
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao 999078, China.
2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao 999078, China. Electronic address: ytwang@umac.mo.
3. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Science, University of Macau, Macao 999078, China. Electronic address: xpchen@umac.mo.
- Publication Type:Journal Article
- Keywords:
Breast Cancer;
Cucurbitacin B;
FAK;
Metastasis;
ROS
- MeSH:
Acetylcysteine;
pharmacology;
Antineoplastic Agents;
pharmacology;
Breast Neoplasms;
enzymology;
metabolism;
pathology;
physiopathology;
Cell Adhesion;
drug effects;
Cell Line, Tumor;
Cell Movement;
drug effects;
Collagen Type I;
metabolism;
Dose-Response Relationship, Drug;
Down-Regulation;
drug effects;
Female;
Fibronectins;
metabolism;
Focal Adhesion Kinase 1;
metabolism;
Humans;
Neoplasm Invasiveness;
pathology;
Neoplasm Metastasis;
pathology;
Paxillin;
metabolism;
Phosphorylation;
drug effects;
Reactive Oxygen Species;
metabolism;
Triterpenes;
antagonists & inhibitors;
chemistry;
pharmacology
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(1):10-19
- CountryChina
- Language:English
-
Abstract:
Metastasis is responsible for the majority of cancer-related deaths and prevention of metastasis remains a big challenge for cancer therapy. Cucurbitacin B (Cuc B) is a natural triterpenoid with potent anticancer activities while its effect on metastasis remains unclear. In the present study, the inhibitory effect and mechanisms of Cuc B on metastasis were investigated in MDA-MB-231 breast cancer cells. The cells were treated with or without Cuc B, and the cytotoxicity was determined by MTT assay. The effect of Cuc B on metastasis was evaluated with wound healing, transwell, and adhesion assays. Furthermore, the adhesion of cancer cells to endothelial cells was determined. The protein expression was determined by Western blotting. Cuc B (< 100 nmol·L) showed no obvious cytotoxicity to MDA-MB-231 cells, but significantly inhibited migration, invasion, and adhesion to Matrigel, fibronectin, type I collagen, and endothelial cells. Cuc B dramatically inhibited the phosphorylation of focal adhesion kinase (FAK) and paxillin in dose- and time-dependent manners. Furthermore, Cuc B induced intracellular reactive oxygen species (ROS) generation, which could be reduced by N-acetyl-l-cysteine (NAC). In addition, NAC pretreatment could reverse Cuc B-induced suppression of migration and adhesion, expression of FAK, but showed no effect on paxillin expression. In summary, Cuc B suppressed ROS-dependent metastasis through FAK pathway in breast cancer MDA-MB-231 cells, demonstrating novel mechanisms for the anticancer effects of Cuc B.
