Cancer-Causing Agent in Cigarette Smoke Blocks Key Protein in Cells

Researchers have uncovered new evidence of a cancer-causing agent present in the gaseous phase of cigarette smoke that inhibits Na,K-ATPase, the sodium-potassium pump essential for the healthy, physiological functioning of cells.

Cigarette smoke (CS) has more than 4,000 components, many of which are linked to the development and progression of lung cancer. Evidence has shown secondhand smoke to be almost as dangerous as primary smoke due to its impact on the cells of the body.

By studying lung cell cultures exposed to CS, the investigators identified a cancer-causing agent called reactive oxygen species (ROS) present in the gaseous phase of CS that disrupts normal cell function. Exposure to the secondhand smoke produced by as little as two cigarettes was found to almost completely inhibit Na,K-ATPase activity within a few hours.

They further examined whether Na,K-ATPase expression correlated with increasing grades of lung adenocarcinoma and survival of patients with smoking history. Immunohistochemical analysis of lung adenocarcinoma tissues revealed reduced Na,K-ATPase expression with increasing tumor grade. Using tissue microarray containing lung adenocarcinomas of patients with known smoking status, high expression of Na,K-ATPase was found to be correlated with better survival.

Overall, reduced competence of the cell's ability to regulate sodium-potassium levels was predictive of cell damage, disease progression and, ultimately, survival. For the first time, CS is shown to be associated with loss of Na,K-ATPase function and expression in lung carcinogenesis, and likely also contributes to disease progression.

"This is critical information with regard to secondhand smoke. [...] Exposure to the gaseous substance alone, which you breathe while standing near a smoker, is sufficient to cause harm," said A. K. Rajasekaran, PhD, lead scientist of the study and Director of the Nemours Center for Childhood Cancer Research (Nemours; Wilmington, DE, USA).

Dr. Lee Goodglick, Associate Professor in the Department of Pathology and Laboratory Medicine, University of California at Los Angeles (UCLA; Los Angeles, CA, USA) and cosenior author of the study, noted, "Few reliable lung cancer biomarkers that could predict survival, treatment options or response to therapy exist today. Even fewer have been recognized where the function of the biomarker is known, yielding important information about the mechanism of action. This study really accomplishes both."

This research, reported online ahead of print February 17, 2012, in the American Journal of Physiology - Lung Cell and Molecular Physiology,is the latest finding in the compendium of evidence that supports protection, especially for children, from exposure to cigarette smoke, and reveals that secondhand smoke may be even more dangerous than previously thought.

Related Links:
Nemours Center for Childhood Cancer Research
University of California at Los Angeles