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Cotylenin A, a Differentiation-inducing Agent, and IFN- Cooperatively Induce Apoptosis and Have an Antitumor Effect on Human Non-Small Cell Lung Carcinoma Cells in Nude Mice¹

Saitama Cancer Center Research Institute, Saitama 362-0806 [Y. H., Y. I., Y. Y-Y., K. A.], and Department of Bioresource Engineering, Yamagata University, Tsuruoka [T. S.], Japan

Cotylenin A, a novel inducer of the differentiation of leukemia cells, and IFN- synergistically inhibited the growth of and induced apoptosis in several human non-small cell lung carcinoma cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptor DR5 were the early genes induced by the combination of cotylenin A and IFN in lung carcinoma cells. Neutralizing antibody to TRAIL inhibited apoptosis, suggesting that cotylenin A and IFN cooperatively induced apoptosis through the TRAIL signaling system. This combined treatment preferentially induced apoptosis in human lung cancer cells while sparing normal lung epithelial cells and significantly inhibited the growth of human lung cancer cells as xenografts without apparent adverse effects, suggesting that this combination may have therapeutic value in treating lung cancer.

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