Rakovina patří bezesporu k nejobávanějším civilizačním nemocem naší doby. Ačkoli příčin transformace normální buňky na rakovinnou může být celá řada a jednotlivé nádory se liší po genetické stránce, jedno mají společné: rakovinné buňky zcela změní úroveň svého metabolismu, aby uspokojily nároky na rychlý buněčný růst a dělení (proliferaci). Příspěvek se snaží popsat složitou problematiku fyziologických rozdílů v metabolismu zdravé a rakovinné buňky a naznačit, jak tyto poznatky použít jako vhodnou zbraň v onkologické léčbě. Vznik a růst zhoubných nádorů je již několik desetiletí předmětem zájmu lékařů a vědců z mnoha oborů. Z hlediska léčby jde především o rozpoznání znaků, které jsou pro rakovinnou buňku jedinečné a které lze využít pro její cílené zničení bez poškození buněk zdravých. A právě jedním z takových univerzálních znaků rakovinných buněk je specifický metabolismus.
Použitá a citovaná literatura:
R. J. DeBerardinis, A. Mancuso, E. Daikhin, I. Nissim, M. Yudkoff, S. Wehrli, C. B. Thompson. Beyond aerobic glycolysis: transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 49, pp. 19345–50, Dec. 2007.
R. J. DeBerardinis, C. B. Thompson. Cellular metabolism and disease: what do metabolic outliers teach us? Cell, vol. 148, no. 6, pp. 1132–44, Mar. 2012.
I. I. Budihardjo, D. L. Walker, P. a Svingen, C. a Buckwalter, S. Desnoyers, S. Eckdahl, G. M. Shah, G. G. Poirier, J. M. Reid, M. M. Ames, S. H. Kaufmann. 6-Aminonicotinamide sensitizes human tumor cell lines to cisplatin. Clinical cancer research : an official journal of the American Association for Cancer Research, vol. 4, no. 1, pp. 117–30, Jan. 1998.
Z. Chen, W. Lu, C. Garcia-Prieto, P. Huang. The Warburg effect and its cancer therapeutic implications. Journal of bioenergetics and biomembranes, vol. 39, no. 3, pp. 267–74, Jun. 2007.
L. M. R. Ferreira. Cancer metabolism: The Warburg effect today. Experimental and Molecular Pathology, vol. 89, no. 3, pp. 372–380, Dec. 2010.
R. Flavin. Fatty acid synthase as a potential therapeutic target in cance. Future oncol., vol. 40, no. 2, pp. 323–332, 2010.
S. Ganapathy-Kanniappan, M. Vali, R. Kunjithapatham, M. Buijs, L. H. Syed, P. P. Rao, S. Ota, B. K. Kwak, R. Loffroy, J. F. Geschwind. 3-bromopyruvate: a new targeted antiglycolytic agent and a promise for cancer therapy. Current pharmaceutical biotechnology, vol. 11, no. 5, pp. 510–7, Aug. 2010.
R. B. Hamanaka, N. S. Chandel. Cell biology. Warburg effect and redox balance. Science (New York, N.Y.), vol. 334, no. 6060, pp. 1219–20, Dec. 2011.
M. G. Vander Heiden, L. C. Cantley, C. B. Thompson. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science (New York, N.Y.), vol. 324, no. 5930, pp. 1029–33, May 2009.
F. P. Herter, S. G. Weissman, H. G. Thompson, G. Hyman, D. S. Martin. Clinical experience with 6-aminonicotinamide. Cancer research, vol. 21, pp. 31–7, Jan. 1961.
T.-S. Ho, Y.-P. Ho, W.-Y. Wong, L. Chi-Ming Chiu, Y.-S. Wong, V. Eng-Choon Ooi. Fatty acid synthase inhibitors cerulenin and C75 retard growth and induce caspase-dependent apoptosis in human melanoma A-375 cells. Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie, vol. 61, no. 9, pp. 578–87, Oct. 2007.
P. P. Hsu, D. M. Sabatini. Cancer cell metabolism: Warburg and beyond. Cell, vol. 134, no. 5, pp. 703–7, Sep. 2008.
T. J. Key. Fruit and vegetables and cancer risk. British journal of cancer, vol. 104, no. 1, pp. 6–11, Jan. 2011.
J. Kim, C. V. Dang. Cancer’s molecular sweet tooth and the Warburg effect. Cancer research, vol. 66, no. 18, pp. 8927–30, Sep. 2006.
H. H. Kim, T. Kim, E. Kim, J. K. Park, S.-J. Park, H. Joo, H. J. Kim. The Mitochondrial Warburg Effect: A Cancer Enigma. Interdisciplinary Bio Central, vol. 1, no. 2, pp. 1–7, Jun. 2009.
K. H. Kim, A. M. Rodriguez, P. M. Carrico, J. A. Melendez. Potential mechanisms for the inhibition of tumor cell growth by manganese superoxide dismutase. Antioxidants & redox signaling, vol. 3, no. 3, pp. 361–73, Jun. 2001.
M. D. Kipling, H. A. Waldron. Percivall Pott and cancer scroti. British journal of industrial medicine, vol. 32, no. 3, pp. 244–6, Aug. 1975.
J. A. Koutcher, http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA409633. 01-May-2002. [Online]. Available: http://oai.dtic.mil/oai/oai?verb=getRecord&metadataPrefix=html&identifier=ADA409633. [Accessed: 06-Jun-2013].
H. Krebs, C. Dang. Energy Boost: The Warburg Effect Returns in a New Theory of Cancer. Nature Reviews Cancer, vol. 96, no. 24, pp. 1805–1806, 2004.
R. L. Krisher, R. S. Prather. A role for the Warburg effect in preimplantation embryo development: metabolic modification to support rapid cell proliferation. Molecular reproduction and development, vol. 79, no. 5, pp. 311–20, May 2012.
F. P. Kuhajda, E. S. Pizer, J. N. Li, N. S. Mani, G. L. Frehywot, C. a Townsend. Synthesis and antitumor activity of an inhibitor of fatty acid synthase. Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 7, pp. 3450–4, Mar. 2000.
A. J. Levine, A. M. Puzio-Kuter. The control of the metabolic switch in cancers by oncogenes and tumor suppressor genes. Science (New York, N.Y.), vol. 330, no. 6009, pp. 1340–4, Dec. 2010.
W. Li, J. Liu, Y. Zhao. PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells. Molecular carcinogenesis, no. November, pp. 1–10, Dec. 2012.
M. López-Lázaro. The Warburg Effect: Why and How do Cancer Cells Activate Glycolysis in the Presence of Oxygen? Science, vol. 8, pp. 305–312, 2008.
S. B. Markowitz, S. M. Levin, A. Miller, A. Morabia. Asbestos, Asbestosis, Smoking and Lung Cancer: New Findings from the North American Insulator Cohort. American journal of respiratory and critical care medicine, Apr. 2013.
S. Matoba, J.-G. Kang, W. D. Patino, A. Wragg, M. Boehm, O. Gavrilova, P. J. Hurley, F. Bunz, P. M. Hwang. P53 Regulates Mitochondrial Respiration. Science (New York, N.Y.), vol. 312, no. 5780, pp. 1650–3, Jun. 2006.
S. Murata, K. Yanagisawa, K. Fukunaga, T. Oda, A. Kobayashi, R. Sasaki, N. Ohkohchi, “Fatty acid synthase inhibitor cerulenin suppresses liver metastasis of colon cancer in mice.,” Cancer science, vol. 101, no. 8, pp. 1861–5, Aug. 2010.
R. K. Murray, D. K. Granner, P. A. Mayes, V. W. Rodwell. Harper’s Illustrated Biochemistry, 26th ed. 2003, p. 700.
A. Najafov, D. R. Alessi. Uncoupling the Warburg effect from cancer. Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 45, pp. 19135–6, Nov. 2010.
E. C. Nakajima, B. Van Houten. Metabolic symbiosis in cancer: Refocusing the Warburg lens. Molecular carcinogenesis, no. November, pp. 1–9, Jan. 2012.
H. Pelicano, D. S. Martin, R.-H. Xu, P. Huang. Glycolysis inhibition for anticancer treatment. Oncogene, vol. 25, no. 34, pp. 4633–46, Aug. 2006.
V. Rottiers and A. M. Näär. MicroRNAs in metabolism and metabolic disorders. Nature reviews. Molecular cell biology, vol. 13, no. 4, pp. 239–50, Apr. 2012.
J. M. Thornburg, K. K. Nelson, B. F. Clem, A. N. Lane, S. Arumugam, A. Simmons, J. W. Eaton, S. Telang, J. Chesney. Targeting aspartate aminotransferase in breast cancer. Breast cancer research : BCR, vol. 10, no. 5, p. R84, Jan. 2008.
O. Warburg. On the Origin of Cancer Cells. Science, vol. 123, no. 3191, pp. 309–314, 1956.
F. Weinberg, N. S. Chandel. Mitochondrial metabolism and cancer. Annals of the New York Academy of Sciences, vol. 1177, pp. 66–73, Oct. 2009.
D. R. Wise, C. B. Thompson. Glutamine addiction: a new therapeutic target in cancer. Trends in biochemical sciences, vol. 35, no. 8, pp. 427–33, Aug. 2010.
N. Wong, J. De Melo, D. Tang. PKM2, a Central Point of Regulation in Cancer Metabolism. International journal of cell biology, vol. 2013, no. Figure 1, p. 242513, Jan. 2013.
Y. Zhao, E. B. Butler, M. Tan. Targeting cellular metabolism to improve cancer therapeutics. Cell death & disease, vol. 4, no. 3, p. e532, Jan. 2013.
There is one feature common to most types of cancer – profound changes in their cellular metabolism that accommodate the high requirements for fast growth and cell division. This change brings about many advantages to the transformed cell and it is also indispensable for its survival and proliferation. This review describes the differences in metabolism between normal and cancerous cells and outlines strategies that could exploit these differences as tools for oncological treatment.