Ouabain enhances lung cancer cell detachment.
A human steroid hormone, ouabain, has been shown to play a role in several types of cancer cell behavior; however, its effects on cancer metastasis are largely unknown. Herein, we demonstrate that sub-toxic concentrations of ouabain facilitate cancer cell detachment from the extracellular matrix in human lung cancer cells. Ouabain at concentrations of 0-10 pM significantly enhanced cell detachment in dose- and time- dependent manners, while having minimal effect on cell viability. The detachment-inducing effect of ouabain was found to be mediated through focal-adhesion kinase and ATP-dependent tyrosine kinase pathways. Alpha-5 and beta-1 integrins were found to be down-regulated in response to ouabain treatment. Since detachment of cancer cells is a prerequisite process for metastasis to begin, these insights benefit our understanding over the molecular basis of cancer biology.
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences and Cell-based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, 10330 Thailand. pithi_chan@yahoo.com.
Thidarat
T
Ruanghirun
Varisa
V
Pongrakhananon
Pithi
P
Chanvorachote
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D010042:Ouabain / Q000378:metabolism* / Q000494:pharmacology
D010042:Ouabain
ATP-dependent tyrosine kinase; Ouabain; cancer metastasis; cell detachment; focal-adhesion kinase H23 cells; lung cancer