Hypoxia-induced activation of the
hypoxia-inducible factor 1 (HIF-1) signaling pathway is frequently observed in solid
tumors and is strongly associated with numerous pathophysiological processes, including the induction of epithelial-mesenchymal transition (EMT), which result in
cancer progression and
metastasis. Thus, inhibiting EMT through the suppression of the HIF-1 pathway may be a promising strategy for anticancer
chemotherapy.
Pien Tze Huang (PZH), a well-established
traditional Chinese medicine has been prescribed for >450 years and has been used for centuries to clinically treat various types of human
cancer. We previously reported that PZH suppresses multiple intracellular signaling pathways and thereby promotes the apoptosis of
cancer cells and the inhibition of cell proliferation and
tumor angiogenesis. In the present study, to further explore the mechanisms underlying the antitumor action of PZH, HCT-8 human colon
carcinoma cells were cultured under hypoxic conditions and the effect of PZH on
hypoxia-induced EMT was assessed.
Hypoxia was found to induce EMT-associated morphological changes in HCT-8 cells, including loss of cell adhesion and the development of spindle-shaped fibroblastoid-like morphology. In addition,
hypoxia was observed to reduce the expression of the epithelial marker
E-cadherin, but increase that of the mesenchymal marker
N-cadherin. In addition,
hypoxia significantly enhanced HCT-8 cell migration and invasion and induced the activation of the HIF-1 pathway. However, treatment of the HCT-8 cells with PZH significantly inhibited the
hypoxia-mediated EMT and HIF-1 signaling. These findings suggest that PZH inhibits
hypoxia-induced
cancer EMT through the suppression of the HIF-1 pathway, which may be one of the molecular mechanisms by which PZH exerts its antitumor activity.