Wnt/β-catenin modulates chronic tobacco smoke exposure-induced acquisition of pulmonary cancer stem cell properties and diallyl trisulfide intervention

Lung cancer is the leading cause of cancer-related death worldwide; tobacco smoke (TS) constitutes the main causes of lung cancer. Acquisition of cancer stem cells (CSCs)-like properties is the essential progression for the initiation of lung cancer. However, the mechanisms for tobacco smoke-induced lung carcinogenesis remain elusive. In the present study, we demonstrated that long-term exposure of human bronchial epithelial (HBE) cells to TS resulted in malignant transformation and acquisition of CSC-like properties. Moreover, Wnt/beta-catenin pathway was involved in acquisition of the CSC-like phenotype during neoplastic transformation of HBE cells induced by TS. Downregulation of beta-catenin reduced the tumorsphere and decreased the protein expression of lung CSCs markers in TS-transformated HBE sphere-forming cells. Furthermore, Diallyl trisulfide (DATS) inhibited the CSCs activity of TS-transformed HBE cells, as well as Wnt/beta-catenin suppression. Activation of Wnt/beta-catenin diminished the inhibitory effects of DATS on TS-induced stemness of HBE cells. Together, the present investigation elucidates the modulation of Wnt/beta-catenin in chronic TS exposure-triggered pulmonary acquisition of CSCs properties and DATS intervention, which may provide new insights into the interventional strategies against lung CSCs.