title: Pien Tze Huang inhibits hypoxia-induced epithelial-mesenchymal transition in human colon carcinoma cells through suppression of the HIF-1 pathway.
abstract: 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.
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Chen
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Aling
authors.initials: A
authors.lastname: Shen
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Yuchen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Youqin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Jiumao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: Rainbow Babies and Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Sferra
authors.affiliation: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Fujian Key Laboratory of Integrative Medicine on Geriatrics, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China ; Postdoctoral Workstation, Zhangzhou Pien Tze Huang Pharmaceutical Co., Ltd., Zhangzhou, Fujian 363000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
keywords: HIF-1 pathway; Pien Tze Huang; colon cancer; epithelial-mesenchymal transition; hypoxia; traditional Chinese medicine