Natural insecticide identified as potential cancer prevention agent for early stage lung cancer

Deguelin may inhibit growth of Akt, an essential molecule in the promotion of precancer

The use of deguelin, a natural plant extract most commonly used as an insecticide in Africa and South American, inhibits the growth of precancerous and cancerous lung cells, with no toxic effects on normal cells, according to a study presented today at the first annual Frontiers in Cancer Prevention Research meeting convened by the American Association for Cancer Research. The role of deguelin as an inhibitor of Akt activation has clinical implications, especially in non-small cell lung cancer (NSCLC), where constant activation of Akt occurs. Akt, or protein kinase B, is recognized as one of the most important molecules that promotes the survival of tumor cells by playing the critical role of controlling the balance between survival and apoptosis (programmed cell death).

The study investigated the effects of deguelin on cells representing different stages of lung cancer, and characterized the ways in which deguelin works on precancerous and cancerous human bronchial epithelial (HBE) cells. Deguelin has been isolated from plants such as Mundulea sericea (Leguminosae), which is native to Africa and South America.

“The results of our study provide evidence for the first time that Akt is essential in the growth of precancerous human bronchial epithelial cell line, and that deguelin can be a potential chemopreventive agent against lung cancer,” according to Ho-Young Lee, Ph.D., lead investigator of the study, which was conducted by researchers at UT M.D. Anderson Cancer Center.

Several studies have shown that Akt provides a critical cell survival signal for tumor progression by adding phosphate to the proteins involved in cell cycle regulation and pre-cell death factors. Results of this study found that the activation of Akt is a common feature in the early stages of cancer and that inhibition of Akt might be a potential target for chemoprevention. Deguelin is an optimal agent for this goal, according to the results of the study, as it selectively blocked the growth of precancerous and cancerous HBE cells by causing cellular death, with no toxic effects on the HBE cells.

“The role of deguelin as an inhibitor of Akt activation has clinical implications, especially in the prevention and treatment of lung cancer, where controlled activation of Akt occurs at a high frequency” said Dr. Lee. “The manipulation of Akt activity alters the sensitivity of NSCLC cells to chemotherapy and irradiation. Therefore, targeting Akt using deguelin may enhance the effectiveness of chemotherapy and radiation therapy and increase the apoptotic potential of NSCLC cells.”

The goal of chemoprevention for lung and other cancers is development of a specifically targeted agent with minimal toxicity that will delay, block or reverse cancer development.

An estimated 169,400 new cases of lung cancer will be diagnosed in 2002, accounting for 13 percent of cancer diagnoses, according to the American Cancer Society. Non-small cell lung cancer accounts for 75 to 80 percent of all lung cancer cases. Lung cancer will claim the lives of more than 154,900 men and women this year, accounting for 28 percent of all cancer deaths. Since 1987, more women have died each year from lung cancer than breast cancer, which, for over 40 years, was the major cause of cancer death in women. It is estimated that approximately 65,700 women will die from lung cancer and 39,600 women will die from breast cancer in 2002.