This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yokota, S.-i. Articles by Nagata, K. Search for Related Content PubMed PubMed Citation Articles by Yokota, S.-i. Articles by Nagata, K.

Benzylidene Lactam Compound, KNK437, a Novel Inhibitor of Acquisition of Thermotolerance and Heat Shock Protein Induction in Human Colon Carcinoma Cells

Takasago Research Laboratories, Research Institute, Kaneka Corporation, Takasago 676-8688, Japan [S. Y., M. K.], and Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan [K. N.]

Cells exposed to heat or other types of stressors transiently synthesize a group of proteins known as heat shock proteins (HSPs). A nonlethal heat treatment can elicit in the cells an ability to resist subsequent lethal heat treatments. We report here that a novel benzylidene lactam compound, KNK437, dose-dependently inhibited the acquisition of thermotolerance and the induction of various HSPs including HSP105, HSP70, and HSP40 in COLO 320DM (human colon carcinoma) cells. The induction of heat-inducible HSP70, which is reported to be involved in the development of thermotolerance, was inhibited at mRNA levels by treatment with KNK437. This compound also inhibited the acquisition of thermotolerance as developed by sodium arsenite. However, it did not increase thermosensitivity in nontolerant cells. The effect of KNK437 was much greater than that of quercetin, a bioflavonoid that was previously reported to inhibit the acquisition of thermotolerance as well as the induction of HSPs. We conclude that this drug is a novel inhibitor of the acquisition of thermotolerance caused by the induction of HSPs.

This article has been cited by other articles:

				C. A. Martin, D. L. Kurkowski, A. M. Valentino, and F. Santiago-Schwarz Increased Intracellular, Cell Surface, and Secreted Inducible Heat Shock Protein 70 Responses Are Triggered during the Monocyte to Dendritic Cell (DC) Transition by Cytokines Independently of Heat Stress and Infection and May Positively Regulate DC Growth J. Immunol., July 1, 2009; 183(1): 388 - 399. [Abstract] [Full Text] [PDF]

				A. A. Gupte, G. L. Bomhoff, J. K. Morris, B. K. Gorres, and P. C. Geiger Lipoic acid increases heat shock protein expression and inhibits stress kinase activation to improve insulin signaling in skeletal muscle from high-fat-fed rats J Appl Physiol, April 1, 2009; 106(4): 1425 - 1434. [Abstract] [Full Text] [PDF]

				G. Kalthur, S. Mutalik, and U. D. Pathirissery Effect of Withaferin A on the Development and Decay of Thermotolerance in B16F1 Melanoma: A Preliminary Study Integr Cancer Ther, March 1, 2009; 8(1): 93 - 97. [Abstract] [PDF]

				A. A. Gupte, G. L. Bomhoff, R. H. Swerdlow, and P. C. Geiger Heat Treatment Improves Glucose Tolerance and Prevents Skeletal Muscle Insulin Resistance in Rats Fed a High-Fat Diet Diabetes, March 1, 2009; 58(3): 567 - 578. [Abstract] [Full Text] [PDF]

				D. C. Carrettiero, I. Hernandez, P. Neveu, T. Papagiannakopoulos, and K. S. Kosik The Cochaperone BAG2 Sweeps Paired Helical Filament- Insoluble Tau from the Microtubule J. Neurosci., February 18, 2009; 29(7): 2151 - 2161. [Abstract] [Full Text] [PDF]

				J.-Y. Lee, Y.-J. Kim, T.-Y. Kim, J.-Y. Koh, and Y.-H. Kim Essential Role for Zinc-Triggered p75NTR Activation in Preconditioning Neuroprotection J. Neurosci., October 22, 2008; 28(43): 10919 - 10927. [Abstract] [Full Text] [PDF]

				M. K. Callahan, M. Garg, and P. K. Srivastava Heat-shock protein 90 associates with N-terminal extended peptides and is required for direct and indirect antigen presentation PNAS, February 5, 2008; 105(5): 1662 - 1667. [Abstract] [Full Text] [PDF]

				P. M. Voorhees, Q. Chen, D. J. Kuhn, G. W. Small, S. A. Hunsucker, J. S. Strader, R. E. Corringham, M. H. Zaki, J. A. Nemeth, and R. Z. Orlowski Inhibition of Interleukin-6 Signaling with CNTO 328 Enhances the Activity of Bortezomib in Preclinical Models of Multiple Myeloma Clin. Cancer Res., November 1, 2007; 13(21): 6469 - 6478. [Abstract] [Full Text] [PDF]

				P. A. Phillips, V. Dudeja, J. A. McCarroll, D. Borja-Cacho, R. K. Dawra, W. E. Grizzle, S. M. Vickers, and A. K. Saluja Triptolide Induces Pancreatic Cancer Cell Death via Inhibition of Heat Shock Protein 70 Cancer Res., October 1, 2007; 67(19): 9407 - 9416. [Abstract] [Full Text] [PDF]

				A. R. A. Villalobos and J. L. Renfro Trimethylamine oxide suppresses stress-induced alteration of organic anion transport in choroid plexus J. Exp. Biol., February 1, 2007; 210(3): 541 - 552. [Abstract] [Full Text] [PDF]

				S. D. Westerheide, T. L. A. Kawahara, K. Orton, and R. I. Morimoto Triptolide, an Inhibitor of the Human Heat Shock Response That Enhances Stress-induced Cell Death J. Biol. Chem., April 7, 2006; 281(14): 9616 - 9622. [Abstract] [Full Text] [PDF]

				M. Kumar and D. Mitra Heat Shock Protein 40 Is Necessary for Human Immunodeficiency Virus-1 Nef-mediated Enhancement of Viral Gene Expression and Replication J. Biol. Chem., December 2, 2005; 280(48): 40041 - 40050. [Abstract] [Full Text] [PDF]

				F. Guo, K. Rocha, P. Bali, M. Pranpat, W. Fiskus, S. Boyapalle, S. Kumaraswamy, M. Balasis, B. Greedy, E. S. M. Armitage, et al. Abrogation of Heat Shock Protein 70 Induction as a Strategy to Increase Antileukemia Activity of Heat Shock Protein 90 Inhibitor 17-Allylamino-Demethoxy Geldanamycin Cancer Res., November 15, 2005; 65(22): 10536 - 10544. [Abstract] [Full Text] [PDF]

				S. D. Westerheide and R. I. Morimoto Heat Shock Response Modulators as Therapeutic Tools for Diseases of Protein Conformation J. Biol. Chem., September 30, 2005; 280(39): 33097 - 33100. [Abstract] [Full Text] [PDF]

				M. W. Graner and D. D. Bigner Chaperone proteins and brain tumors: Potential targets and possible therapeutics Neuro-oncol, July 1, 2005; 7(3): 260 - 278. [Abstract] [PDF]

				M. Koishi, S.'i. Yokota, T. Mae, Y. Nishimura, S. Kanamori, N. Horii, K. Shibuya, K. Sasai, and M. Hiraoka The Effects of KNK437, a Novel Inhibitor of Heat Shock Protein Synthesis, on the Acquisition of Thermotolerance in a Murine Transplantable Tumor in Vivo Clin. Cancer Res., January 1, 2001; 7(1): 215 - 219. [Abstract] [Full Text]