The impact of chronic exposure to cigarette and waterpipe smoke extracts on telomeres, telomerase, and cancer progression.

INTRODUCTION: Tobacco smoking remains a leading cause of many life-threatening diseases, particularly lung cancer. Waterpipe smoking has rapidly gained popularity worldwide, while research on this tobacco form remains limited. Tobacco smoking has been linked to the shortening of telomeres and activation of telomerase, important regulators of genomic stability and cancer progression. However, the direct impact of whole-smoke exposure on telomere dynamics and its relationship with cancer progression remains minimally explored, and this requires suitable experimental systems. METHODS: This study aims to demonstrate an experimental procedure to enable prolonged exposure of lung cancer cells (A549) to sub-toxic concentrations of cigarette and waterpipe smoke extracts, and to investigate in those cells the effects on telomere length, telomerase activity, and cancer progression. We also checked telomere length, epithelial-to-mesenchymal transition (EMT) markers, and migration in two other colon (HCT116) and breast cancer (MCF7) cell lines. RESULTS: After 12 weeks of exposure, there was a significant decrease in relative telomere length in heterogeneous/parents of A549 cells with waterpipe exposure, and a significant increase in telomerase activity with cigarette exposure. Chronic exposure to both smoke extracts also led to a significant upregulation in the expression of the SNAI2 mesenchymal marker in both heterogeneous populations and single-cell-derived colonies. Additionally, chronic exposure to cigarette smoke extract significantly enhanced migration in single-cell-derived colonies. Comparable results were seen in the colonies of colon and breast cancer cell lines. DISCUSSION: Our findings revealed that chronic smoke exposure disrupts telomere dynamics particularly in lung cancer cells and triggers transcriptional EMT changes that might contribute to cancer progression in lung, breast, and colon cancer cells, offering new insights into a potential link between tobacco smoke, telomere dysfunction, and cancer progression.