This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fribley, A.
Right arrow Articles by Wang, C.-Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fribley, A.
Right arrow Articles by Wang, C.-Y.

Next Article 

Molecular and Cellular Biology, November 2004, p. 9695-9704, Vol. 24, No. 22
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.22.9695-9704.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Proteasome Inhibitor PS-341 Induces Apoptosis through Induction of Endoplasmic Reticulum Stress-Reactive Oxygen Species in Head and Neck Squamous Cell Carcinoma Cells

Andrew Fribley,1,2 Qinghua Zeng,1 and Cun-Yu Wang1,2*

Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences,1 Program in Oral Health Sciences, School of Dentistry, University of Michigan, Ann Arbor, Michigan2

Received 25 April 2004/ Returned for modification 26 May 2004/ Accepted 28 July 2004

PS-341, also known as Velcade or Bortezomib, represents a new class of anticancer drugs which has been shown to potently inhibit the growth and/or progression of human cancers, including head and neck squamous cell carcinoma (HNSCC). Although it has been logically hypothesized that NF-{kappa}B is a major target of PS-341, the underlying mechanism by which PS-341 inhibits tumor cell growth is unclear. Here we found that PS-341 potently activated the caspase cascade and induced apoptosis in human HNSCC cell lines. Although PS-341 could inhibit NF-{kappa}B activation, the inhibition of NF-{kappa}B was not sufficient to initiate apoptosis in HNSCC cells. Using biochemical and microarray approaches, we found that proteasome inhibition by PS-341 induced endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in HNSCC cells. The inhibition of ROS significantly suppressed caspase activation and apoptosis induced by PS-341. Consistently, PS-341 could not induce the ER stress-ROS in PS-341-resistant HNSCC cells. Taken together, our results suggest that in addition to the abolishment of the prosurvival NF-{kappa}B, PS-341 might directly induce apoptosis by activating proapoptotic ER stress-ROS signaling cascades in HNSCC cells, providing novel insights into the PS-341-mediated antitumor activity.

* Corresponding author. Mailing address: Laboratory of Molecular Signaling and Apoptosis, Department of Biologic and Materials Sciences, University of Michigan, 1011 N. University Ave., Ann Arbor, MI 48109-1078. Phone: (734) 615-4386. Fax: (734) 647-2110. E-mail: cunywang{at}umich.edu.

Molecular and Cellular Biology, November 2004, p. 9695-9704, Vol. 24, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.22.9695-9704.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Golden, E. B., Lam, P. Y., Kardosh, A., Gaffney, K. J., Cadenas, E., Louie, S. G., Petasis, N. A., Chen, T. C., Schonthal, A. H. (2009). Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. Blood 113: 5927-5937 [Abstract] [Full Text]  
  • Milani, M., Rzymski, T., Mellor, H. R., Pike, L., Bottini, A., Generali, D., Harris, A. L. (2009). The Role of ATF4 Stabilization and Autophagy in Resistance of Breast Cancer Cells Treated with Bortezomib. Cancer Res. 69: 4415-4423 [Abstract] [Full Text]  
  • Schewe, D. M., Aguirre-Ghiso, J. A. (2009). Inhibition of eIF2{alpha} Dephosphorylation Maximizes Bortezomib Efficiency and Eliminates Quiescent Multiple Myeloma Cells Surviving Proteasome Inhibitor Therapy. Cancer Res. 69: 1545-1552 [Abstract] [Full Text]  
  • Pagnan, G., Di Paolo, D., Carosio, R., Pastorino, F., Marimpietri, D., Brignole, C., Pezzolo, A., Loi, M., Galietta, L. J.V., Piccardi, F., Cilli, M., Nico, B., Ribatti, D., Pistoia, V., Ponzoni, M. (2009). The Combined Therapeutic Effects of Bortezomib and Fenretinide on Neuroblastoma Cells Involve Endoplasmic Reticulum Stress Response. Clin. Cancer Res. 15: 1199-1209 [Abstract] [Full Text]  
  • Little, J. L., Wheeler, F. B., Koumenis, C., Kridel, S. J. (2008). Disruption of crosstalk between the fatty acid synthesis and proteasome pathways enhances unfolded protein response signaling and cell death. Molecular Cancer Therapeutics 7: 3816-3824 [Abstract] [Full Text]  
  • Fels, D. R., Ye, J., Segan, A. T., Kridel, S. J., Spiotto, M., Olson, M., Koong, A. C., Koumenis, C. (2008). Preferential Cytotoxicity of Bortezomib toward Hypoxic Tumor Cells via Overactivation of Endoplasmic Reticulum Stress Pathways. Cancer Res. 68: 9323-9330 [Abstract] [Full Text]  
  • Ahn, H. J., Hernandez, C. M., Levenson, J. M., Lubin, F. D., Liou, H.-C., Sweatt, J. D. (2008). c-Rel, an NF-{kappa}B family transcription factor, is required for hippocampal long-term synaptic plasticity and memory formation. Learn. Mem. 15: 539-549 [Abstract] [Full Text]  
  • Chen, Z., Ricker, J. L., Malhotra, P. S., Nottingham, L., Bagain, L., Lee, T. L., Yeh, N. T., Van Waes, C. (2008). Differential bortezomib sensitivity in head and neck cancer lines corresponds to proteasome, nuclear factor-{kappa}B and activator protein-1 related mechanisms. Molecular Cancer Therapeutics 7: 1949-1960 [Abstract] [Full Text]  
  • Chen, J.-J., Chou, C.-W., Chang, Y.-F., Chen, C.-C. (2008). Proteasome Inhibitors Enhance TRAIL-Induced Apoptosis through the Intronic Regulation of DR5: Involvement of NF-{kappa}B and Reactive Oxygen Species-Mediated p53 Activation. J. Immunol. 180: 8030-8039 [Abstract] [Full Text]  
  • Li, C., Li, R., Grandis, J. R., Johnson, D. E. (2008). Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells. Molecular Cancer Therapeutics 7: 1647-1655 [Abstract] [Full Text]  
  • Lei, P., Abdelrahim, M., Cho, S. D., Liu, S., Chintharlapalli, S., Safe, S. (2008). 1,1-Bis(3'-indolyl)-1-(p-substituted phenyl)methanes inhibit colon cancer cell and tumor growth through activation of c-jun N-terminal kinase. Carcinogenesis 29: 1139-1147 [Abstract] [Full Text]  
  • Kandasamy, K., Kraft, A. S. (2008). Proteasome inhibitor PS-341 (VELCADE) induces stabilization of the TRAIL receptor DR5 mRNA through the 3'-untranslated region. Molecular Cancer Therapeutics 7: 1091-1100 [Abstract] [Full Text]  
  • Chauhan, D., Singh, A., Brahmandam, M., Podar, K., Hideshima, T., Richardson, P., Munshi, N., Palladino, M. A., Anderson, K. C. (2008). Combination of proteasome inhibitors bortezomib and NPI-0052 trigger in vivo synergistic cytotoxicity in multiple myeloma. Blood 111: 1654-1664 [Abstract] [Full Text]  
  • Colado, E., Alvarez-Fernandez, S., Maiso, P., Martin-Sanchez, J., Vidriales, M. B., Garayoa, M., Ocio, E. M., Montero, J. C., Pandiella, A., San Miguel, J. F. (2008). The effect of the proteasome inhibitor bortezomib on acute myeloid leukemia cells and drug resistance associated with the CD34+ immature phenotype. haematol 93: 57-66 [Abstract] [Full Text]  
  • Nieto-Miguel, T., Fonteriz, R. I., Vay, L., Gajate, C., Lopez-Hernandez, S., Mollinedo, F. (2007). Endoplasmic Reticulum Stress in the Proapoptotic Action of Edelfosine in Solid Tumor Cells. Cancer Res. 67: 10368-10378 [Abstract] [Full Text]  
  • Li, X., Peng, C., Li, L., Ming, M., Yang, D., Le, W. (2007). Glial Cell-Derived Neurotrophic Factor Protects Against Proteasome Inhibition-Induced Dopamine Neuron Degeneration by Suppression of Endoplasmic Reticulum Stress and Caspase-3 Activation. Journals of Gerontology Series A: Biological Sciences and Medical Sciences 62: 943-950 [Abstract] [Full Text]  
  • Rahmani, M., Davis, E. M., Crabtree, T. R., Habibi, J. R., Nguyen, T. K., Dent, P., Grant, S. (2007). The Kinase Inhibitor Sorafenib Induces Cell Death through a Process Involving Induction of Endoplasmic Reticulum Stress. Mol. Cell. Biol. 27: 5499-5513 [Abstract] [Full Text]  
  • Ding, W.-X., Ni, H.-M., Gao, W., Yoshimori, T., Stolz, D. B., Ron, D., Yin, X.-M. (2007). Linking of Autophagy to Ubiquitin-Proteasome System Is Important for the Regulation of Endoplasmic Reticulum Stress and Cell Viability. Am. J. Pathol. 171: 513-524 [Abstract] [Full Text]  
  • Wang, H.-Q., Du, Z.-X., Zhang, H.-Y., Gao, D.-X. (2007). Different Induction of GRP78 and CHOP as a Predictor of Sensitivity to Proteasome Inhibitors in Thyroid Cancer Cells. Endocrinology 148: 3258-3270 [Abstract] [Full Text]  
  • Miller, C. P., Ban, K., Dujka, M. E., McConkey, D. J., Munsell, M., Palladino, M., Chandra, J. (2007). NPI-0052, a novel proteasome inhibitor, induces caspase-8 and ROS-dependent apoptosis alone and in combination with HDAC inhibitors in leukemia cells. Blood 110: 267-277 [Abstract] [Full Text]  
  • Liu, X., Yue, P., Chen, S., Hu, L., Lonial, S., Khuri, F. R., Sun, S.-Y. (2007). The Proteasome Inhibitor PS-341 (Bortezomib) Up-Regulates DR5 Expression Leading to Induction of Apoptosis and Enhancement of TRAIL-Induced Apoptosis Despite Up-Regulation of c-FLIP and Survivin Expression in Human NSCLC Cells. Cancer Res. 67: 4981-4988 [Abstract] [Full Text]  
  • Dragovich, T., Gordon, M., Mendelson, D., Wong, L., Modiano, M., Chow, H.-H. S., Samulitis, B., O'Day, S., Grenier, K., Hersh, E., Dorr, R. (2007). Phase I Trial of Imexon in Patients With Advanced Malignancy. JCO 25: 1779-1784 [Abstract] [Full Text]  
  • Kubota, Y., Kinoshita, K., Suetomi, K., Fujimori, A., Takahashi, S. (2007). Mcl-1 Depletion in Apoptosis Elicited by Ionizing Radiation in Peritoneal Resident Macrophages of C3H Mice. J. Immunol. 178: 2923-2931 [Abstract] [Full Text]  
  • Ding, W.-X., Ni, H.-M., Chen, X., Yu, J., Zhang, L., Yin, X.-M. (2007). A coordinated action of Bax, PUMA, and p53 promotes MG132-induced mitochondria activation and apoptosis in colon cancer cells. Molecular Cancer Therapeutics 6: 1062-1069 [Abstract] [Full Text]  
  • Lorch, J. H., Thomas, T. O., Schmoll, H.-J. (2007). Bortezomib Inhibits Cell-Cell Adhesion and Cell Migration and Enhances Epidermal Growth Factor Receptor Inhibitor-Induced Cell Death in Squamous Cell Cancer. Cancer Res. 67: 727-734 [Abstract] [Full Text]  
  • Ge, Y., Montano, I., Rustici, G., Freebern, W. J., Haggerty, C. M., Cui, W., Ponciano-Jackson, D., Chandramouli, G. V. R., Gardner, E. R., Figg, W. D., Abu-Asab, M., Tsokos, M., Jackson, S. H., Gardner, K. (2006). Selective leukemic-cell killing by a novel functional class of thalidomide analogs. Blood 108: 4126-4135 [Abstract] [Full Text]  
  • Fribley, A. M., Evenchik, B., Zeng, Q., Park, B. K., Guan, J. Y., Zhang, H., Hale, T. J., Soengas, M. S., Kaufman, R. J., Wang, C.-Y. (2006). Proteasome Inhibitor PS-341 Induces Apoptosis in Cisplatin-resistant Squamous Cell Carcinoma Cells by Induction of Noxa. J. Biol. Chem. 281: 31440-31447 [Abstract] [Full Text]  
  • Carayol, N., Chen, J., Yang, F., Jin, T., Jin, L., States, D., Wang, C.-Y. (2006). A Dominant Function of IKK/NF-{kappa}B Signaling in Global Lipopolysaccharide-induced Gene Expression. J. Biol. Chem. 281: 31142-31151 [Abstract] [Full Text]  
  • Ishii, Y., Pirkmaier, A., Alvarez, J. V., Frank, D. A., Keselman, I., Logothetis, D., Mandeli, J., O'Connell, M. J., Waxman, S., Germain, D. (2006). Cyclin d1 overexpression and response to bortezomib treatment in a breast cancer model.. JNCI J Natl Cancer Inst 98: 1238-1247 [Abstract] [Full Text]  
  • Mulhern, M. L., Madson, C. J., Danford, A., Ikesugi, K., Kador, P. F., Shinohara, T. (2006). The unfolded protein response in lens epithelial cells from galactosemic rat lenses.. IOVS 47: 3951-3959 [Abstract] [Full Text]  
  • Yu, C., Friday, B. B., Lai, J.-P., Yang, L., Sarkaria, J., Kay, N. E., Carter, C. A., Roberts, L. R., Kaufmann, S. H., Adjei, A. A. (2006). Cytotoxic synergy between the multikinase inhibitor sorafenib and the proteasome inhibitor bortezomib in vitro: induction of apoptosis through Akt and c-Jun NH2-terminal kinase pathways.. Molecular Cancer Therapeutics 5: 2378-2387 [Abstract] [Full Text]  
  • Dolcet, X., Llobet, D., Encinas, M., Pallares, J., Cabero, A., Schoenenberger, J. A., Comella, J. X., Matias-Guiu, X. (2006). Proteasome Inhibitors Induce Death but Activate NF-{kappa}B on Endometrial Carcinoma Cell Lines and Primary Culture Explants. J. Biol. Chem. 281: 22118-22130 [Abstract] [Full Text]  
  • Canfield, S. E., Zhu, K., Williams, S. A., McConkey, D. J. (2006). Bortezomib inhibits docetaxel-induced apoptosis via a p21-dependent mechanism in human prostate cancer cells.. Molecular Cancer Therapeutics 5: 2043-2050 [Abstract] [Full Text]  
  • Sheng, X., Hu, Z., Lu, H., Wang, X., Baluska, F., Samaj, J., Lin, J. (2006). Roles of the Ubiquitin/Proteasome Pathway in Pollen Tube Growth with Emphasis on MG132-Induced Alterations in Ultrastructure, Cytoskeleton, and Cell Wall Components. Plant Physiol. 141: 1578-1590 [Abstract] [Full Text]  
  • Koumenis, C., Wouters, B. G. (2006). "Translating" Tumor Hypoxia: Unfolded Protein Response (UPR)-Dependent and UPR-Independent Pathways. Mol Cancer Res 4: 423-436 [Abstract] [Full Text]  
  • Obeng, E. A., Carlson, L. M., Gutman, D. M., Harrington, W. J. Jr, Lee, K. P., Boise, L. H. (2006). Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells. Blood 107: 4907-4916 [Abstract] [Full Text]  
  • Yeung, B. H. Y., Huang, D.-C., Sinicrope, F. A. (2006). PS-341 (Bortezomib) Induces Lysosomal Cathepsin B Release and a Caspase-2-dependent Mitochondrial Permeabilization and Apoptosis in Human Pancreatic Cancer Cells. J. Biol. Chem. 281: 11923-11932 [Abstract] [Full Text]  
  • Nawrocki, S. T., Carew, J. S., Pino, M. S., Highshaw, R. A., Andtbacka, R. H.I., Dunner, K. Jr., Pal, A., Bornmann, W. G., Chiao, P. J., Huang, P., Xiong, H., Abbruzzese, J. L., McConkey, D. J. (2006). Aggresome disruption: a novel strategy to enhance bortezomib-induced apoptosis in pancreatic cancer cells.. Cancer Res. 66: 3773-3781 [Abstract] [Full Text]  
  • Yanamandra, N., Colaco, N. M., Parquet, N. A., Buzzeo, R. W., Boulware, D., Wright, G., Perez, L. E., Dalton, W. S., Beaupre, D. M. (2006). Tipifarnib and Bortezomib Are Synergistic and Overcome Cell Adhesion-Mediated Drug Resistance in Multiple Myeloma and Acute Myeloid Leukemia. Clin. Cancer Res. 12: 591-599 [Abstract] [Full Text]  
  • Vodanovic-Jankovic, S., Hari, P., Jacobs, P., Komorowski, R., Drobyski, W. R. (2006). NF-{kappa}B as a target for the prevention of graft-versus-host disease: comparative efficacy of bortezomib and PS-1145. Blood 107: 827-834 [Abstract] [Full Text]  
  • Fernandez, Y., Miller, T. P., Denoyelle, C., Esteban, J. A., Tang, W.-H., Bengston, A. L., Soengas, M. S. (2006). Chemical Blockage of the Proteasome Inhibitory Function of Bortezomib: IMPACT ON TUMOR CELL DEATH. J. Biol. Chem. 281: 1107-1118 [Abstract] [Full Text]  
  • Zou, W., Yue, P., Lin, N., He, M., Zhou, Z., Lonial, S., Khuri, F. R., Wang, B., Sun, S.-Y. (2006). Vitamin C Inactivates the Proteasome Inhibitor PS-341 in Human Cancer Cells. Clin. Cancer Res. 12: 273-280 [Abstract] [Full Text]  
  • Dasmahapatra, G., Rahmani, M., Dent, P., Grant, S. (2006). The tyrphostin adaphostin interacts synergistically with proteasome inhibitors to induce apoptosis in human leukemia cells through a reactive oxygen species (ROS)-dependent mechanism. Blood 107: 232-240 [Abstract] [Full Text]  
  • Perez-Galan, P., Roue, G., Villamor, N., Montserrat, E., Campo, E., Colomer, D. (2006). The proteasome inhibitor bortezomib induces apoptosis in mantle-cell lymphoma through generation of ROS and Noxa activation independent of p53 status. Blood 107: 257-264 [Abstract] [Full Text]  
  • Nawrocki, S. T., Carew, J. S., Dunner, K. Jr., Boise, L. H., Chiao, P. J., Huang, P., Abbruzzese, J. L., McConkey, D. J. (2005). Bortezomib Inhibits PKR-Like Endoplasmic Reticulum (ER) Kinase and Induces Apoptosis via ER Stress in Human Pancreatic Cancer Cells. Cancer Res. 65: 11510-11519 [Abstract] [Full Text]  
  • Nawrocki, S. T., Carew, J. S., Pino, M. S., Highshaw, R. A., Dunner, K. Jr., Huang, P., Abbruzzese, J. L., McConkey, D. J. (2005). Bortezomib Sensitizes Pancreatic Cancer Cells to Endoplasmic Reticulum Stress-Mediated Apoptosis. Cancer Res. 65: 11658-11666 [Abstract] [Full Text]  
  • Chen, J.-J., Huang, W.-C., Chen, C.-C. (2005). Transcriptional Regulation of Cyclooxygenase-2 in Response to Proteasome Inhibitors Involves Reactive Oxygen Species-mediated Signaling Pathway and Recruitment of CCAAT/Enhancer-binding Protein {delta} and CREB-binding Protein. Mol. Biol. Cell 16: 5579-5591 [Abstract] [Full Text]  
  • Zhu, Z., Ramos, J., Kampa, K., Adimoolam, S., Sirisawad, M., Yu, Z., Chen, D., Naumovski, L., Lopez, C. D. (2005). Control of ASPP2/53BP2L Protein Levels by Proteasomal Degradation Modulates p53 Apoptotic Function. J. Biol. Chem. 280: 34473-34480 [Abstract] [Full Text]  
  • Obeng, E. A., Boise, L. H. (2005). Caspase-12 and Caspase-4 Are Not Required for Caspase-dependent Endoplasmic Reticulum Stress-induced Apoptosis. J. Biol. Chem. 280: 29578-29587 [Abstract] [Full Text]  
  • Jiang, H.-Y., Wek, R. C. (2005). Phosphorylation of the {alpha}-Subunit of the Eukaryotic Initiation Factor-2 (eIF2{alpha}) Reduces Protein Synthesis and Enhances Apoptosis in Response to Proteasome Inhibition. J. Biol. Chem. 280: 14189-14202 [Abstract] [Full Text]  
  • Chauhan, D., Hideshima, T., Mitsiades, C., Richardson, P., Anderson, K. C. (2005). Proteasome inhibitor therapy in multiple myeloma. Molecular Cancer Therapeutics 4: 686-692 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»