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  3. Polyhexamethylene guanidine phosphate induces epithelial-to-mesenchymal transition and cancer stem cell-like properties via Wnt/β-catenin signaling in human bronchial epithelial cells

Polyhexamethylene guanidine phosphate induces epithelial-to-mesenchymal transition and cancer stem cell-like properties via Wnt/β-catenin signaling in human bronchial epithelial cells

  • Ecotoxicol Environ Saf. 2025 Mar 1:292:117930. doi: 10.1016/j.ecoenv.2025.117930.
Gi Ho Lee 1,  Seung Yeon Lee 1,  Yong-Wook Baek 2,  Jungyun Lim 2,  Kyu Hyuck Chung 3,  Hye Gwang Jeong 4
Affiliations

Affiliations

  • 1 College of Pharmacy, Chungnam National University, Daejeon 34134, South Korea.
  • 2 Humidifier Disinfectant Health Center, Environmental Health Research, National Institute of Environmental Research, Incheon 22689, South Korea.
  • 3 College of Pharmacy, Kyungsung University, Busan 48434, South Korea.
  • 4 College of Pharmacy, Chungnam National University, Daejeon 34134, South Korea. Electronic address: hgjeong@cnu.ac.kr.
PMID: 39986058 DOI: 10.1016/j.ecoenv.2025.117930
Abstract

Inhalation exposure to polyhexamethylene guanidine phosphate (PHMG-p), a primary component of humidifier disinfectants, has been linked to interstitial lung disease and potential carcinogenic effects. This study aimed to investigate epithelial cell transformation and the underlying molecular mechanisms by examining the properties of epithelial-mesenchymal transition (EMT) and Cancer Stem Cells (CSCs) following prolonged exposure to PHMG-p. Beas-2B human bronchial epithelial cells were treated with 0.125-0.5 µg/ml PHMG-p for over 55 passages, resulting in approximately a 1.2-fold increase in proliferation and a 2-fold enhancement in wound healing, migration, and invasion. Long-term exposure induced morphological changes in Beas-2B, which adopted a spindle-shaped appearance, and displayed enhanced expression of EMT markers, including N-Cadherin, Vimentin, Twist, and Snail (approximately 1.5- to 3.5-fold). Culturing these cells in a Cancer stem cell medium further confirmed neoplastic transformation and the induction of CSC properties in long-term PHMG-p-treated cells. Additionally, expression levels of CSC phenotypic markers (CD44, CD133, ABCG2, and ALDH1A1) and stemness markers (SOX2, OCT4, Nanog, and KLF4) increased during PHMG-p-induced carcinogenesis. Moreover, increased Reactive Oxygen Species (ROS) production and expression of β-catenin indicated the involvement of these signaling molecules during carcinogenesis. Collectively, our findings suggest that chronic exposure to PHMG-p, even at relatively low concentrations, can induce neoplastic transformation through the acquisition of EMT, stemness, and CSC phenotypes, potentially linked to the endogenous ROS and Wnt/β-catenin signaling pathway.

Keywords

Cancer stem cells; Epithelial-mesenchymal transition; Polyhexamethylene guanidine phosphate; Reactive oxygen species; Wnt/β-catenin signaling pathway.

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