The traditional Tibetan medicine Yukyung Karne exhibits a potent anti-metastatic activity by inhibiting the epithelial to mesenchymal transition and cell migration

Abstract

Background: In Traditional Tibetan medicine, Yukyung Karne has been used for the treatment of ovarian cancer. Though Yukyung Karne has been reported to be clinically effective, the molecular mechanism of its anti-metstatic action remains elusive. Methods: The cytotoxic property of Yukyung Karne was evaluated by crystal violet staining while its ability to induce ceramide production was analyzed by sphingomyelinase assay. The anti-metastatic property was investigated using adhesion, invasion, migration and colony formation assays. The effect of Yukyung Karne on the expression of extracellular matrix components, and epithelial and mesenchymal markers were evaluated by confocal microscopy and western blotting. Results: Yukyung Karne exhibited a strong anti-metastatic property by significantly reducing the invasion, migration and colony formation ability of ovarian cancer cells. Besides it inhibited the levels of biomarkers involved in epithelial to mesenchymal transition such as down-regulation of vimentin and N-cadherin and up-regulation of epithelial E-cadherin. Yukyung Karne also induced the neutral sphingomyelinase II (nSMNaseII) enzyme activity that is known to hydrolyze sphingomyelins into pro-apoptotic intracellular molecule ceramide. Conclusions: The study provides some compelling evidences supporting the anti-metastatic potential of Yukyung Karne which strongly suggests its possible usage as a promising alternative medicine. Thus, Yukyung Karne may be used as an anticancer and anti-metastatic agent along with other conventional anticancer therapeutics to increase their efficacy.