Lung Cancer Linked to High Dietary Levels of Inorganic Phosphates

Five-week-old male K-rasLA1 lung cancer model mice and six-week-old male urethane-induced lung cancer model mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for four weeks. At the end of this period, all mice were sacrificed, and lung cancer development was evaluated by diverse methods.

Results published in the January 1, 2009, online edition of the American Journal of Respiratory and Critical Care Medicine revealed that the high Pi diet increased lung tumor progression and growth compared with the normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter-2b protein levels in the lungs. High dietary consumption of Pi stimulated Akt activity in the lungs while suppressing the protein levels of tumor suppressor phosphatases. Since it can block apoptosis, and thereby promote cell survival, Akt has been implicated as a major factor in many types of cancer. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-rasLA1 mice.

"Our study indicates that increased intake of inorganic phosphates strongly stimulates lung cancer development in mice, and suggests that dietary regulation of inorganic phosphates may be critical for lung cancer treatment as well as prevention,” said senior author Dr. Myung-Haing Cho, professor of toxicology at Seoul National University. "Phosphate is an essential nutrient to living organisms, and can activate some signals. This study demonstrates that high intake of inorganic phosphates may strongly stimulate lung cancer development by altering those (signaling) pathways.”

"Lung cancer is a disease of uncontrolled cell proliferation in lung tissue, and disruption of signaling pathways in those tissues can confer a normal cell with malignant properties,” said Dr. Cho. "Deregulation of only a small set of pathways can confer a normal cell with malignant properties, and these pathways are regulated in response to nutrient availability and, consequently, cell proliferation, and growth.”

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Seoul National University