Induction of the mitochondria apoptosis pathway by phytohemagglutinin erythroagglutinating in human lung cancer cells.

Wei-Ting Kuo, Yung-Jen Ho, Shyh-Ming Kuo, Feng-Huei Lin, Fuu-Jen Tsai, Yueh-Sheng Chen, Guo-Chung Dong, Chun-Hsu Yao

Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.

Annals of surgical oncology 2011 Mar

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Deregulation of apoptosis will influence the balance of cell proliferation and cell death, resulting in various fatal diseases that can include cancer. In prior research reports related to cancer therapy, phytohemagglutinin, a lectin extracted from red kidney beans, demonstrated the ability to inhibit the growth of human cancer cells. However, one of its isoforms, erythroagglutinating, has yet to be evaluated on its anticancer effects. PHA-E was used to induce apoptosis of A-549 lung cancer cells and the possible signal transduction pathway was elucidated, as measured by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, G6PD release assay, flow cytometry, and Western blot analysis. PHA-E treatment caused a dose-dependent increase of cell growth inhibition and cytotoxicity on A-549 cells. In annexin V/propidium iodide [i.e., PI] and TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)/PI assay, we found that the rate of apoptotic cells was raised as the concentration of PHA-E increased. Treatment of A-549 cells with PHA-E resulted in enhancing the release of cytochrome c, which thus activated an increase in caspase 9 and caspase 3, the upregulation of Bax and Bad, the downregulation of Bcl-2 and phosphorylated Bad, and finally the inhibition of the epidermal growth factor receptor and its downstream signal pathway PI3K/Akt and MEK/ERK. PHA-E can induce growth inhibition and cytotoxicity of lung cancer cells, which is mediated through an activation of the mitochondria apoptosis pathway. These results suggest that PHA-E can be developed into a new therapeutic treatment that can be applied as an effective anti-lung cancer drug in the near future.

Citation

Wei-Ting Kuo, Yung-Jen Ho, Shyh-Ming Kuo, Feng-Huei Lin, Fuu-Jen Tsai, Yueh-Sheng Chen, Guo-Chung Dong, Chun-Hsu Yao. Induction of the mitochondria apoptosis pathway by phytohemagglutinin erythroagglutinating in human lung cancer cells. Annals of surgical oncology. 2011 Mar;18(3):848-56