Tauroursodeoxycholic acid reduces the invasion of MDA-MB-231 cells by modulating matrix metalloproteinases 7 and 13.
Tauroursodeoxycholic acid (TUDCA) is a conjugated form of UDCA that modulates several signaling pathways and acts as a chemical chaperone to relieve endoplasmic reticulum (ER) stress. The present study showed that TUDCA reduced the invasion of the MDA-MB-231 metastatic breast cancer cell line under normoxic and hypoxic conditions using anin vitroinvasion assay. Quantitative polymerase chain reaction assay revealed that the reduced invasion following TUDCA treatment was associated with a decreased expression of matrix metalloproteinase (MMP)-7 and -13, which play important roles in invasion and metastasis. Inhibitors and short hairpin RNAs were used to show that the effect of TUDCA in the reduction of invasion appeared to be dependent on the protein kinase RNA-like ER kinase pathway, a downstream ER stress signaling pathway. Thus, TUDCA is a candidate anti-metastatic agent to target the ER stress pathway.
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea; Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
Ga-Young
GY
Park
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
Yu Kyeong
YK
Han
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
Jeong Yoon
JY
Han
Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan 619-953, Republic of Korea.
Chang Geun
CG
Lee
endoplasmic reticulum stress; invasion; matrix metalloproteinase; protein kinase RNA-like endoplasmic reticulum kinase; tauroursodeoxycholic acid