Editors' ChoiceCancer therapy

Pseudomonas Gives Cancer Cells the Blues

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Science's STKE  12 Nov 2002:
Vol. 2002, Issue 158, pp. tw416
DOI: 10.1126/stke.2002.158.tw416

Yamada et al. demonstrated that a bacterial protein involved in electron transport can trigger apoptosis in melanoma cells, an observation with intriguing implications for the development of new approaches to treating cancer. Reports that bacterial infections can sometimes elicit remission of certain forms of cancer date back over 100 years. Indeed, Mycobacterium bovis bacillus Calmette-Guerin is commonly used in the topical therapy of bladder cancer. Cancer remission after exposure to microbial pathogens, or their products, has traditionally been ascribed to stimulation of the immune response. Yamada et al. demonstrated, however, that purified azurin, a redox protein cloned from the bacterium Pseudomonas aeruginosa, triggered apoptosis in cultured human melanoma cells and inhibited growth of human melanoma cells transplanted into nude mice. Azurin's cytotoxicity depended both on its electron transport capacity and on expression of p53 by the cell line. Azurin increased nuclear and cytosolic p53 content and enhanced mitochondrial accumulation of the proapoptotic protein Bax. The authors used Western analysis on subcellular fractions of azurin-treated melanoma cells, as well as fluorescence microscopy after microinjection of labeled azurin, to localize azurin not only to the cytoplasm, but also to the nucleus. Western analysis of fractions collected from glycerol gradients indicated that azurin formed a complex with p53; experiments involving pharmacological inhibition of protein synthesis suggested that this complex stabilized p53. The apparent lack of toxicity associated with purified azurin when injected into nude mice, in contrast to live bacteria, suggest that azurin and similar proteins might form the basis for the development of new antineoplastic agents.

T. Yamada, M. Goto, V. Punj, O. Zaborina, M. L. Chen, K. Kimbara, D. Majumdar, E. Cunningham, T. K. Das Gupta, A. M. Chakrabarty, Bacterial redox protein azurin, tumor suppressor protein p53, and regression of cancer. Proc. Natl. Acad. Sci. U.S.A. 99,14098-14102 (2002). [Abstract] [Full Text]

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