Fax: +313-576-8389.
Cancer Therapy
TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer†
Article first published online: 4 JUN 2008
DOI: 10.1002/ijc.23610
Copyright © 2008 Wiley-Liss, Inc.
Additional Information
How to Cite
Wang, Z., Song, W., Aboukameel, A., Mohammad, M., Wang, G., Banerjee, S., Kong, D., Wang, S., Sarkar, F. H. and Mohammad, R. M. (2008), TW-37, a small-molecule inhibitor of Bcl-2, inhibits cell growth and invasion in pancreatic cancer. Int. J. Cancer, 123: 958–966. doi: 10.1002/ijc.23610
- †
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.
Publication History
- Issue published online: 12 JUN 2008
- Article first published online: 4 JUN 2008
- Manuscript Accepted: 11 MAR 2008
- Manuscript Received: 7 JUL 2007
Funded by
- National Cancer Institute, NIH. Grant Number: R01CA109389
- NIH. Grant Number: 5R01CA101870
- NIH. Grant Number: P30CA22453
- NIH. Grant Number: U19CA11317
- Department of Defense Breast Cancer Program. Grant Number: BC0009140
References
- 1,,,,,. Cancer statistics, 2007. CA Cancer J Clin 2007; 57: 43–66.Direct Link:
- 2,,,,,. Nonpeptidic small-molecule inhibitor of Bcl-2 and Bcl-XL, (−)-Gossypol, enhances biological effect of genistein against BxPC-3 human pancreatic cancer cell line. Pancreas 2005; 31: 317–24.
- 3,,,,,. Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol Cancer Ther 2006; 5: 1387–95.
- 4,. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 2007; 26: 1324–37.
- 5,,,,,. Cisplatin-induced antitumor activity is potentiated by the soy isoflavone genistein in BxPC-3 pancreatic tumor xenografts. Cancer 2006; 106: 1260–8.Direct Link:
- 6,,,,. Molecular prognostic markers in pancreatic cancer: a systematic review. Eur J Cancer 2005; 41: 2213–36.
- 7,,,,,,,,,,,, et al. A novel BH3 mimetic reveals a mitogen-activated protein kinase-dependent mechanism of melanoma cell death controlled by p53 and reactive oxygen species. Cancer Res 2006; 66: 11348–59.
- 8,,,,,,,. Antiangiogenic effect of TW37, a small-molecule inhibitor of Bcl-2. Cancer Res 2006; 66: 8698–706.
- 9,,,,,,,,. Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res 2007; 13: 2226–35.
- 10,,,,,. Bcl-2 over-expression enhances NF-kappaB activity and induces mmp-9 transcription in human MCF7(ADR) breast-cancer cells. Int J Cancer 2000; 86: 188–96.Direct Link:
- 11,,,,,,,,,,,, et al. Bcl-2 acts in a proangiogenic signaling pathway through nuclear factor-kappaB and CXC chemokines. Cancer Res 2005; 65: 5063–9.
- 12,,,,,,,,,,,, et al. Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem 2006; 49: 6139–42.
- 13,,,,,. Down-regulation of Notch-1 inhibits invasion by inactivation of nuclear factor-{kappa}B, vascular endothelial growth factor, and matrix metalloproteinase-9 in pancreatic cancer cells. Cancer Res 2006; 66: 2778–84.
- 14,,,,,,,,,,. Epidermal growth factor receptor-related protein inhibits cell growth and invasion in pancreatic cancer. Cancer Res 2006; 66: 7653–60.
- 15,,,,,. Suppression of IP3-mediated calcium release and apoptosis by Bcl-2 involves the participation of protein phosphatase 1. Mol Cell Biochem 2007; 295: 153–65.
- 16,,,,. Down-regulation of Forkhead Box M1 transcription factor leads to the inhibition of invasion and angiogenesis of pancreatic cancer cells. Cancer Res 2007; 67: 8293–300.
- 17,,,,,,,,,. Establishment of a human pancreatic tumor xenograft model: potential application for preclinical evaluation of novel therapeutic agents. Pancreas 1998; 16: 19–25.
- 18,,,,,,. Bcl-w promotes gastric cancer cell invasion by inducing matrix metalloproteinase-2 expression via phosphoinositide 3-kinase, Akt, and Sp1. Cancer Res 2006; 66: 4991–5.
- 19,,,,,,,,,,. Bcl-2 expression correlates with lymphovascular invasion and long-term prognosis in breast cancer. Breast Cancer Res Treat 2006; 99: 77–83.
- 20,,,,,,,. Bcl-2 promotes invasion and lung metastasis by inducing matrix metalloproteinase-2. Cancer Res 2005; 65: 5554–60.
- 21,,. IKK beta is required for Bcl-2-mediated NF-kappa B activation in ventricular myocytes. J Biol Chem 2002; 277: 38676–82.
- 22,,,. Bcl-2 activates the transcription factor NFkappaB through the degradation of the cytoplasmic inhibitor IkappaBalpha. J Biol Chem 1998; 273: 23946–51.
- 23,,,,. Bcl-2/Bcl-xL mediate ROS production in pancreatic cancer cells leading to the inhibition of apoptosis (Abstract 4581). 97th AACR Annual Meeting, Los Angeles 2007.
- 24
- 25,,,,,,. BCL-2 functions as an activator of the AKT signaling pathway in pancreatic cancer. J Cell Biochem 2007; 102: 1171–9.Direct Link:
- 26. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res 2007; 13: 1076–82.
- 27. Multiple myeloma: lusting for NF-kappaB. Cancer Cell 2007; 12: 95–7.
- 28,. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 2000; 36: 1621–30.
- 29,,,,,,,,,,,. Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue. Am J Pathol 2005; 166: 1173–86.
- 30,,,,. Histologic features of venous invasion, expression of vascular endothelial growth factor and matrix metalloproteinase-2 and matrix metalloproteinase-9, and the relation with liver metastasis in pancreatic cancer. Pancreas 2002; 24: 169–78.
- 31,,,. Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-kappaB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation. Oncogene 2004; 23: 9247–58.
- 32,,. Evodiamine abolishes constitutive and inducible NF-kappaB activation by inhibiting IkappaBalpha kinase activation, thereby suppressing NF-kappaB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion. J Biol Chem 2005; 280: 17203–12.

1097-0215/asset/olbannerleft.jpg?v=1&s=45719cd7de57873027993264fcc568b335a8cd56)
1097-0215/asset/olbannerright.jpg?v=1&s=5e0fba63c1309b3036eb9215a0e1e83dd02efd19)
1097-0215/asset/cover.gif?v=1&s=9bea5e55449dab2cff7ad3b06277cc9745417a23)