TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer Conflict of Interest: University of Michigan has filed a patent on TW-37, which has been licensed by Ascenta Therapeutics Inc. University of Michigan and Dr. Shaomeng Wang own equity in Ascenta. Dr. Shaomeng Wang also serves as a consultant for Ascenta and is the principal investigator on research contract from Ascenta to University of Michigan.
dc.contributor.author | Wang, Zhiwei | en_US |
dc.contributor.author | Song, Wen | en_US |
dc.contributor.author | Aboukameel, Amro | en_US |
dc.contributor.author | Mohammad, Mussop | en_US |
dc.contributor.author | Wang, Guoping | en_US |
dc.contributor.author | Banerjee, Sanjeev | en_US |
dc.contributor.author | Kong, Dejuan | en_US |
dc.contributor.author | Wang, Shaomeng | en_US |
dc.contributor.author | Sarkar, Fazlul H. | en_US |
dc.contributor.author | Mohammad, Ramzi M. | en_US |
dc.date.accessioned | 2008-07-01T14:07:03Z | |
dc.date.available | 2009-09-02T14:40:29Z | en_US |
dc.date.issued | 2008-08-15 | en_US |
dc.identifier.citation | Wang, Zhiwei; Song, Wen; Aboukameel, Amro; Mohammad, Mussop; Wang, Guoping; Banerjee, Sanjeev; Kong, Dejuan; Wang, Shaomeng; Sarkar, Fazlul H.; Mohammad, Ramzi M. (2008). "TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer Conflict of Interest: University of Michigan has filed a patent on TW-37, which has been licensed by Ascenta Therapeutics Inc. University of Michigan and Dr. Shaomeng Wang own equity in Ascenta. Dr. Shaomeng Wang also serves as a consultant for Ascenta and is the principal investigator on research contract from Ascenta to University of Michigan. ." International Journal of Cancer 123(4): 958-966. <http://hdl.handle.net/2027.42/60216> | en_US |
dc.identifier.issn | 0020-7136 | en_US |
dc.identifier.issn | 1097-0215 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/60216 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=18528859&dopt=citation | en_US |
dc.description.abstract | Bcl-2 family of proteins plays critical roles in human cancers, including pancreatic cancer, suggesting that the discovery of specific agents targeting Bcl-2 family proteins would be extremely valuable for pancreatic cancer therapy. We have previously reported the synthesis and characterization of TW-37, which seems to be a negative regulator of Bcl-2. In this investigation, we tested our hypothesis whether TW-37 could be an effective inhibitor of cell growth, invasion and angiogenesis in pancreatic cancer cells. Using multiple cellular and molecular approaches such as MTT assay, apoptosis enzyme-linked immunosorbent assay, real-time reverse transcription-polymerase chain reaction, Western blotting, electrophoretic mobility shift assay for measuring DNA binding activity of NF-ΚB, migration, invasion and angiogenesis assays, we found that TW-37, in nanomolar concentrations, inhibited cell growth in a dose- and time-dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-ΚB, and downregulation of NF-ΚB downstream genes such as MMP-9 and VEGF , resulting in the inhibition of pancreatic cancer cell migration, invasion and angiogenesis in vitro and caused antitumor activity in vivo . From these results, we conclude that TW-37 is a potent inhibitor of progression of pancreatic cancer cells, which could be due to attenuation of Bcl-2 cellular signaling processes. Our findings provide evidence showing that TW-37 could act as a small-molecule Bcl-2 inhibitor on well-characterized pancreatic cancer cells in culture as well as when grown as tumor in a xenograft model. We also suggest that TW-37 could be further developed as a potential therapeutic agent for the treatment of pancreatic cancer. © 2008 Wiley-Liss, Inc. | en_US |
dc.format.extent | 809478 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Cancer Research, Oncology and Pathology | en_US |
dc.title | TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer Conflict of Interest: University of Michigan has filed a patent on TW-37, which has been licensed by Ascenta Therapeutics Inc. University of Michigan and Dr. Shaomeng Wang own equity in Ascenta. Dr. Shaomeng Wang also serves as a consultant for Ascenta and is the principal investigator on research contract from Ascenta to University of Michigan. | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Oncology and Hematology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationum | Department of Internal Medicine, Pharmacology and Medicinal Chemistry, University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI | en_US |
dc.contributor.affiliationother | Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Internal Medicine, Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Internal Medicine, Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Internal Medicine, Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI | en_US |
dc.contributor.affiliationother | Department of Internal Medicine, Division of Hematology and Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI ; Fax: +313-576-8389. ; Department of Internal Medicine, Karmanos Cancer Institute, Wayne State University School of Medicine, 732 HWCRC, 4100 John R. Street, Detroit, MI 48201 | en_US |
dc.identifier.pmid | 18528859 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/60216/1/23610_ftp.pdf | |
dc.identifier.doi | http://dx.doi.org/10.1002/ijc.23610 | en_US |
dc.identifier.source | International Journal of Cancer | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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