Health Effects of Smoking

Tobacco smoke has been linked to promotion and progression of many cancers such as lung, head and neck, pancreatic, and breast cancers. We showed that nicotine, a main addictive compound in tobacco smoke, induces the expression of galectin-3 in a breast cancer cell line and in primary tumors from breast cancer patients. Nicotine-induced up regulation of galectin-3 is due to an increased expression of α9 isoform of nicotinic acetylcholine receptor, which activates transcription factor STAT3 that in turn, physically binds to galectin-3 promoter and induces transcription of galectin-3. Intracellular galectin-3 increased mitochondrial integrity and suppressed chemotherapeutic-induced apoptosis of breast cancer cell. Moreover, nicotine induced enrichment of side population cells with cancer stem cell-like properties was modulated by galectin-3 expression and could be significantly reduced by transient knock down of LGALS3 and its upstream signaling molecules STAT3 and cx9nAChR. Thus, galectin-3 or its upstream signaling molecule STAT3 or cx9nAChR could be a potential target to prevent nicotine-induced chemoresistance in breast cancer.  [PUBMED]