| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vol. 273, Issue 3, 1769-1775, January 16, 1998
From the Isothiocyanates have strong chemopreventive
properties against many carcinogen-induced cancers in experimental
animal models. Here, we report that phenylmethyl isocyacyanate
(PMITC) and phenylethyl isothio- cyanate (PEITC) induced sustained
c-Jun N-terminal kinase (JNK) activation in a
dose-dependent manner. The sustained JNK activation caused
by isothiocyanates was associated with apoptosis induction in various
cell types. An inhibitor of the caspase/interleukin-1
Molecular Mechanisms of c-Jun N-terminal Kinase-mediated
Apoptosis Induced by Anticarcinogenic Isothiocyanates
,,
Department of Microbiology and Immunology,
Baylor College of Medicine, Houston, Texas 77030 and the
¶ Department of Pharmaceutics and Pharmacodynamics, College of
Pharmacy, University of Illinois, Chicago, Illinois 60612
-converting enzyme blocked isothiocyanate-induced apoptosis without inhibiting the
JNK activation, which suggests that JNK activation by isothiocyanates is an event that is independent or upstream of the activation of
caspase/interleukin-1-converting enzyme proteases. PEITC-induced apoptosis was suppressed by interfering with the JNK pathway with a
dominant-negative mutant of JNK1 or MEKK1 (JNK1(APF) and MEKK1(KR), respectively), implying that the JNK pathway is required for apoptotic signaling. Isothiocyanate-induced JNK activation was blocked by the
antioxidants 2-mercaptoethanol and
N-acetyl-L-cysteine, suggesting that the death
signaling was triggered by oxidative stress. Overexpression of Bcl-2
suppressed PEITC-induced JNK activation. In addition, Bcl-2 and
Bcl-xL suppressed PEITC-induced apoptosis, but failed to
protect cells from death induced by overexpression of activated JNK1.
These results suggest that Bcl-2 and Bcl-xL are upstream of
JNK. Taken together, our results indicate (i) that JNK mediates PMITC-
and PEITC-induced apoptosis and (ii) that PMITC and PEITC may have
chemotherapeutic functions besides their chemopreventive functions.
Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Rubio, J. Quintana, J. L. Eiroa, J. Triana, and F. Estevez Acetyl derivative of quercetin 3-methyl ether-induced cell death in human leukemia cells is amplified by the inhibition of ERK Carcinogenesis, October 1, 2007; 28(10): 2105 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Mi, X. Wang, S. Govind, B. L. Hood, T. D. Veenstra, T. P. Conrads, D. T. Saha, R. Goldman, and F.-L. Chung The Role of Protein Binding in Induction of Apoptosis by Phenethyl Isothiocyanate and Sulforaphane in Human Non-Small Lung Cancer Cells Cancer Res., July 1, 2007; 67(13): 6409 - 6416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hu, J. Straub, D. Xiao, S. V. Singh, H.-S. Yang, N. Sonenberg, and J. Vatsyayan Phenethyl Isothiocyanate, a Cancer Chemopreventive Constituent of Cruciferous Vegetables, Inhibits Cap-Dependent Translation by Regulating the Level and Phosphorylation of 4E-BP1 Cancer Res., April 15, 2007; 67(8): 3569 - 3573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao and S. V. Singh Phenethyl Isothiocyanate Inhibits Angiogenesis In vitro and Ex vivo Cancer Res., March 1, 2007; 67(5): 2239 - 2246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, K. L. Lew, Y. Zeng, H. Xiao, S. W. Marynowski, R. Dhir, and S. V. Singh Phenethyl isothiocyanate-induced apoptosis in PC-3 human prostate cancer cells is mediated by reactive oxygen species-dependent disruption of the mitochondrial membrane potential Carcinogenesis, November 1, 2006; 27(11): 2223 - 2234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Zhang, S. Loganathan, I. Humphreys, and S. K. Srivastava Benzyl Isothiocyanate-Induced DNA Damage Causes G2/M Cell Cycle Arrest and Apoptosis in Human Pancreatic Cancer Cells J. Nutr., November 1, 2006; 136(11): 2728 - 2734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Thomson, K. K. Brown, J. M. Pullar, and M. B. Hampton Phenethyl Isothiocyanate Triggers Apoptosis in Jurkat Cells Made Resistant by the Overexpression of Bcl-2. Cancer Res., July 1, 2006; 66(13): 6772 - 6777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Xu, G. Shen, X. Yuan, J.-h. Kim, A. Gopalkrishnan, Y.-S. Keum, S. Nair, and A.-N. T. Kong ERK and JNK signaling pathways are involved in the regulation of activator protein 1 and cell death elicited by three isothiocyanates in human prostate cancer PC-3 cells Carcinogenesis, March 1, 2006; 27(3): 437 - 445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Yang, M. Jhanwar-Uniyal, J. Schwartz, C. C. Conaway, H. D. Halicka, F. Traganos, and F.-L. Chung N-Acetylcysteine Conjugate of Phenethyl Isothiocyanate Enhances Apoptosis in Growth-Stimulated Human Lung Cells Cancer Res., September 15, 2005; 65(18): 8538 - 8547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Traka, A. V. Gasper, J. A. Smith, C. J. Hawkey, Y. Bao, and R. F. Mithen Transcriptome Analysis of Human Colon Caco-2 Cells Exposed to Sulforaphane J. Nutr., August 1, 2005; 135(8): 1865 - 1872. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xiao, Y. Zeng, S. Choi, K. L. Lew, J. B. Nelson, and S. V. Singh Caspase-Dependent Apoptosis Induction by Phenethyl Isothiocyanate, a Cruciferous Vegetable-Derived Cancer Chemopreventive Agent, Is Mediated by Bak and Bax Clin. Cancer Res., April 1, 2005; 11(7): 2670 - 2679. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. P. Collett and F. C. Campbell Curcumin induces c-jun N-terminal kinase-dependent apoptosis in HCT116 human colon cancer cells Carcinogenesis, November 1, 2004; 25(11): 2183 - 2189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N.-A. Pham, J. W. Jacobberger, A. D. Schimmer, P. Cao, M. Gronda, and D. W. Hedley The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice Mol. Cancer Ther., October 1, 2004; 3(10): 1239 - 1248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Smith, E. K. Lund, M. L. Parker, R. G. Clarke, and I. T. Johnson Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells Carcinogenesis, August 1, 2004; 25(8): 1409 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, C. S. Johnson, D. L. Trump, and S. V. Singh Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells Mol. Cancer Ther., May 1, 2004; 3(5): 567 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Pullar, S. J. Thomson, M. J. King, C. I. Turnbull, R. G. Midwinter, and M. B. Hampton The chemopreventive agent phenethyl isothiocyanate sensitizes cells to Fas-mediated apoptosis Carcinogenesis, May 1, 2004; 25(5): 765 - 772. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Miyoshi, K. Uchida, T. Osawa, and Y. Nakamura A Link between Benzyl Isothiocyanate-Induced Cell Cycle Arrest and Apoptosis: Involvement of Mitogen-Activated Protein Kinases in the Bcl-2 Phosphorylation Cancer Res., March 15, 2004; 64(6): 2134 - 2142. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-R. Kim, R. Hu, Y.-S. Keum, V. Hebbar, G. Shen, S. S. Nair, and A-N. T. Kong Effects of Glutathione on Antioxidant Response Element-Mediated Gene Expression and Apoptosis Elicited by Sulforaphane Cancer Res., November 1, 2003; 63(21): 7520 - 7525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. K. Srivastava, D. Xiao, K. L. Lew, P. Hershberger, D. M. Kokkinakis, C. S. Johnson, D. L. Trump, and S. V. Singh Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo Carcinogenesis, October 1, 2003; 24(10): 1665 - 1670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. W.Y. Lui, A. L. Wentzel, D. Xiao, K. L. Lew, S. V. Singh, and J. R. Grandis Requirement of a carbon spacer in benzyl isothiocyanate-mediated cytotoxicity and MAPK activation in head and neck squamous cell carcinoma Carcinogenesis, October 1, 2003; 24(10): 1705 - 1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hu, B. R. Kim, C. Chen, V. Hebbar, and A.-N.T. Kong The roles of JNK and apoptotic signaling pathways in PEITC-mediated responses in human HT-29 colon adenocarcinoma cells Carcinogenesis, August 1, 2003; 24(8): 1361 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Vivo, W. Liu, and V. C. Broaddus c-Jun N-terminal Kinase Contributes to Apoptotic Synergy Induced by Tumor Necrosis Factor-related Apoptosis-inducing Ligand plus DNA Damage in Chemoresistant, p53 Inactive Mesothelioma Cells J. Biol. Chem., July 3, 2003; 278(28): 25461 - 25467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao, S. K. Srivastava, K. L. Lew, Y. Zeng, P. Hershberger, C. S. Johnson, D. L. Trump, and S. V. Singh Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits proliferation of human prostate cancer cells by causing G2/M arrest and inducing apoptosis Carcinogenesis, May 1, 2003; 24(5): 891 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Smith, R. Mithen, and I. T. Johnson Effects of Brassica vegetable juice on the induction of apoptosis and aberrant crypt foci in rat colonic mucosal crypts in vivo Carcinogenesis, March 1, 2003; 24(3): 491 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Kassie, M. Uhl, S. Rabot, B. Grasl-Kraupp, R. Verkerk, M. Kundi, M. Chabicovsky, R. Schulte-Hermann, and S. Knasmuller Chemoprevention of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced colonic and hepatic preneoplastic lesions in the F344 rat by cruciferous vegetables administered simultaneously with the carcinogen Carcinogenesis, February 1, 2003; 24(2): 255 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cuadrado, L. F. Garcia-Fernandez, L. Gonzalez, Y. Suarez, A. Losada, V. Alcaide, T. Martinez, J. M. Fernandez-Sousa, J. M. Sanchez-Puelles, and A. Munoz AplidinTM Induces Apoptosis in Human Cancer Cells via Glutathione Depletion and Sustained Activation of the Epidermal Growth Factor Receptor, Src, JNK, and p38 MAPK J. Biol. Chem., January 3, 2003; 278(1): 241 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. J. Lee, J. H. Kim, J. Chen, and J. J. Song Enhancement of Metabolic Oxidative Stress-Induced Cytotoxicity by the Thioredoxin Inhibitor 1-Methylpropyl 2-Imidazolyl Disulfide Is Mediated through the ASK1-SEK1-JNK1 Pathway Mol. Pharmacol., December 1, 2002; 62(6): 1409 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-R. Chen, J. Han, R. Kori, A.-N. T. Kong, and T.-H. Tan Phenylethyl Isothiocyanate Induces Apoptotic Signaling via Suppressing Phosphatase Activity against c-Jun N-terminal Kinase J. Biol. Chem., October 11, 2002; 277(42): 39334 - 39342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R.K. Sticha, P. M.J. Kenney, G. Boysen, H. Liang, X. Su, M. Wang, P. Upadhyaya, and S. S. Hecht Effects of benzyl isothiocyanate and phenethyl isothiocyanate on DNA adduct formation by a mixture of benzo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in A/J mouse lung Carcinogenesis, September 1, 2002; 23(9): 1433 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Hecht, P. Upadhyaya, M. Wang, R. L. Bliss, E. J. McIntee, and P. M.J. Kenney Inhibition of lung tumorigenesis in A/J mice by N-acetyl-S-(N-2-phenethylthiocarbamoyl)-L-cysteine and myo-inositol, individually and in combination Carcinogenesis, September 1, 2002; 23(9): 1455 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, T. L. Zimmerman, S. Thevananther, H.-Y. Lee, J. M. Kurie, and S. J. Karpen Interleukin-1beta -mediated Suppression of RXR:RAR Transactivation of the Ntcp Promoter Is JNK-dependent J. Biol. Chem., August 23, 2002; 277(35): 31416 - 31422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Lennon, M. Ramauge, A. Dessouroux, and M. Pierre MAP Kinase Cascades Are Activated in Astrocytes and Preadipocytes by 15-Deoxy-Delta 12-14-prostaglandin J2 and the Thiazolidinedione Ciglitazone through Peroxisome Proliferator Activator Receptor gamma -independent Mechanisms Involving Reactive Oxygenated Species J. Biol. Chem., August 9, 2002; 277(33): 29681 - 29685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xiao and S. V. Singh Phenethyl Isothiocyanate-induced Apoptosis in p53-deficient PC-3 Human Prostate Cancer Cell Line Is Mediated by Extracellular Signal-regulated Kinases Cancer Res., July 1, 2002; 62(13): 3615 - 3619. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fimognari, M. Nusse, R. Cesari, R. Iori, G. Cantelli-Forti, and P. Hrelia Growth inhibition, cell-cycle arrest and apoptosis in human T-cell leukemia by the isothiocyanate sulforaphane Carcinogenesis, April 1, 2002; 23(4): 581 - 586. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, M. Kawakami, A. Yoshihiro, N. Miyoshi, H. Ohigashi, K. Kawai, T. Osawa, and K. Uchida Involvement of the Mitochondrial Death Pathway in Chemopreventive Benzyl Isothiocyanate-induced Apoptosis J. Biol. Chem., March 1, 2002; 277(10): 8492 - 8499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-M. Yang, C. C. Conaway, J. W. Chiao, C.-X. Wang, S. Amin, J. Whysner, W. Dai, J. Reinhardt, and F.-L. Chung Inhibition of Benzo(a)pyrene-induced Lung Tumorigenesis in A/J Mice by Dietary N-Acetylcysteine Conjugates of Benzyl and Phenethyl Isothiocyanates during the Postinitiation Phase Is Associated with Activation of Mitogen-activated Protein Kinases and p53 Activity and Induction of Apoptosis Cancer Res., January 1, 2002; 62(1): 2 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D'Agostini, R. M. Balansky, A. Izzotti, R. A. Lubet, G. J. Kelloff, and S. De Flora Modulation of apoptosis by cigarette smoke and cancer chemopreventive agents in the respiratory tract of rats Carcinogenesis, March 1, 2001; 22(3): 375 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-L. Chung, C.C. Conaway, C.V. Rao, and B. S. Reddy Chemoprevention of colonic aberrant crypt foci in Fischer rats by sulforaphane and phenethyl isothiocyanate Carcinogenesis, December 1, 2000; 21(12): 2287 - 2291. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mandlekar, R. Yu, T.-H. Tan, and A.-N. T. Kong Activation of Caspase-3 and c-Jun NH2-terminal Kinase-1 Signaling Pathways in Tamoxifen-induced Apoptosis of Human Breast Cancer Cells Cancer Res., November 1, 2000; 60(21): 5995 - 6000. [Abstract] [Full Text]
|
|
|
|
|
|
P. Rose, K. Faulkner, G. Williamson, and R. Mithen 7-Methylsulfinylheptyl and 8-methylsulfinyloctyl isothiocyanates from watercress are potent inducers of phase II enzymes Carcinogenesis, November 1, 2000; 21(11): 1983 - 1988. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-W. Soh, Y. Mao, M.-G. Kim, R. Pamukcu, H. Li, G. A. Piazza, W. J. Thompson, and I. B. Weinstein Cyclic GMP Mediates Apoptosis Induced by Sulindac Derivatives via Activation of c-Jun NH2-Terminal Kinase 1 Clin. Cancer Res., October 1, 2000; 6(10): 4136 - 4141. [Abstract] [Full Text]
|
|
|
|
|
|
K. R.K. Sticha, M. E. Staretz, M. Wang, H. Liang, P. M.J. Kenney, and S. S. Hecht Effects of benzyl isothiocyanate and phenethyl isothiocyanate on benzo[a]pyrene metabolism and DNA adduct formation in the A/J mouse Carcinogenesis, September 1, 2000; 21(9): 1711 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Lakics, A. E. Medvedev, S. Okada, and S. N. Vogel Inhibition of LPS-induced Cytokines by Bcl-xL in a Murine Macrophage Cell Line J. Immunol., September 1, 2000; 165(5): 2729 - 2737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells Carcinogenesis, June 1, 2000; 21(6): 1175 - 1182. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gamet-Payrastre, P. Li, S. Lumeau, G. Cassar, M.-A. Dupont, S. Chevolleau, N. Gasc, J. Tulliez, and F. Tercé Sulforaphane, a Naturally Occurring Isothiocyanate, Induces Cell Cycle Arrest and Apoptosis in HT29 Human Colon Cancer Cells Cancer Res., March 1, 2000; 60(5): 1426 - 1433. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Nakamura, H. Ohigashi, S. Masuda, A. Murakami, Y. Morimitsu, Y. Kawamoto, T. Osawa, M. Imagawa, and K. Uchida Redox Regulation of Glutathione S-Transferase Induction by Benzyl Isothiocyanate: Correlation of Enzyme Induction with the Formation of Reactive Oxygen Intermediates Cancer Res., January 1, 2000; 60(2): 219 - 225. [Abstract] [Full Text]
|
|
|
|
|
|
Y.-R. Chen, G. Zhou, and T.-H. Tan c-Jun N-Terminal Kinase Mediates Apoptotic Signaling Induced by N-(4-Hydroxyphenyl)retinamide Mol. Pharmacol., December 1, 1999; 56(6): 1271 - 1279. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Bugaud, F. Nadal-Wollbold, S. Levy-Toledano, J.-P. Rosa, and M. Bryckaert Regulation of c-Jun-NH2 Terminal Kinase and Extracellular-Signal Regulated Kinase in Human Platelets Blood, December 1, 1999; 94(11): 3800 - 3805. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Satomi, S. Miyamoto, and M. N. Gould Induction of AP-1 activity by perillyl alcohol in breast cancer cells Carcinogenesis, October 1, 1999; 20(10): 1957 - 1961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Reyland, S. M. Anderson, A. A. Matassa, K. A. Barzen, and D. O. Quissell Protein Kinase C delta Is Essential for Etoposide-induced Apoptosis in Salivary Gland Acinar Cells J. Biol. Chem., July 2, 1999; 274(27): 19115 - 19123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. I. Shifrin and P. Anderson Trichothecene Mycotoxins Trigger a Ribotoxic Stress Response That Activates c-Jun N-terminal Kinase and p38 Mitogen-activated Protein Kinase and Induces Apoptosis J. Biol. Chem., May 14, 1999; 274(20): 13985 - 13992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Zhou, S. C. Lee, Z. Yao, and T.-H. Tan Hematopoietic Progenitor Kinase 1 Is a Component of Transforming Growth Factor beta -induced c-Jun N-terminal Kinase Signaling Cascade J. Biol. Chem., May 7, 1999; 274(19): 13133 - 13138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T.-H. Wang, D. M. Popp, H.-S. Wang, M. Saitoh, J. G. Mural, D. C. Henley, H. Ichijo, and J. Wimalasena Microtubule Dysfunction Induced by Paclitaxel Initiates Apoptosis through Both c-Jun N-terminal Kinase (JNK)-dependent and -Independent Pathways in Ovarian Cancer Cells J. Biol. Chem., March 19, 1999; 274(12): 8208 - 8216. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yao, G. Zhou, X. S. Wang, A. Brown, K. Diener, H. Gan, and T.-H. Tan A Novel Human STE20-related Protein Kinase, HGK, That Specifically Activates the c-Jun N-terminal Kinase Signaling Pathway J. Biol. Chem., January 22, 1999; 274(4): 2118 - 2125. [Abstract] [Full Text] [PDF]
|
|
|
