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Ouabain enhances lung cancer cell detachment
Thidarat Ruanghirun1, Varisa Pongrakhananon, Pithi Chanvorachote
1Department 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.
Abstract:
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.
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