Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wnt/β-Catenin Pathways
作者： Lulu Farhana , Marcia I. Dawson , Jayanta K. Das , Farhan Murshed , Zebin Xia
DOI: 10.1155/2012/796729
关键词:
摘要: Pancreatic carcinoma has a dismal prognosis as it often presents locally advanced or metastatic. We have found that exposure to adamantyl-substituted retinoid-related (ARR) compounds 3-Cl-AHPC and AHP3 resulted in growth inhibition apoptosis induction PANC-1, Capan-2, MiaPaCa-2 pancreatic cancer cell lines. In addition, inhibited induced spheres derived from the CD44+/CD24+ (CD133+/EpCAM+) stem-like population isolated 3-Cl-AHPC-induced was preceded by decreasing expression of IGF-1R, cyclin D1, β-catenin, activated Notch-1 Decreased IGF-1R PANC-1 proliferation, enhanced 3-Cl-AHPC-mediated apoptosis, significantly decreased sphere formation. Wnt/β-catenin pathway indicated β-catenin nuclear localization activation transcription factor TCF/LEF. Knockdown using sh-RNA also cells. Thus, induce cells may serve an important potential therapeutic agent treatment cancer.
hindawi.com参考文章(45)
Shi-Yong Sun, Ping Yue, Roshantha A. S. Chandraratna, Yohannes Tesfaigzi, Waun K. Hong, Reuben Lotan, Dual mechanisms of action of the retinoid CD437: nuclear retinoic acid receptor-mediated suppression of squamous differentiation and receptor-independent induction of apoptosis in UMSCC22B human head and neck squamous cell carcinoma cells. Molecular Pharmacology. ,vol. 58, pp. 508- 514 ,(2000) , 10.1124/MOL.58.3.508
Lulu Farhana, Marcia I. Dawson, Mark Leid, Li Wang, David D. Moore, Gang Liu, Zeben Xia, Joseph A. Fontana, Adamantyl-Substituted Retinoid-Related Molecules Bind Small Heterodimer Partner and Modulate the Sin3A Repressor Cancer Research. ,vol. 67, pp. 318- 325 ,(2007) , 10.1158/0008-5472.CAN-06-2164
Nikolaos A. Dallas, Ling Xia, Fan Fan, Michael J. Gray, Puja Gaur, George van Buren, Shaija Samuel, Michael P. Kim, Sherry J. Lim, Lee M. Ellis, Chemoresistant Colorectal Cancer Cells, the Cancer Stem Cell Phenotype, and Increased Sensitivity to Insulin-like Growth Factor-I Receptor Inhibition Cancer Research. ,vol. 69, pp. 1951- 1957 ,(2009) , 10.1158/0008-5472.CAN-08-2023
Gang Zeng, Matt Germinaro, Amanda Micsenyi, Navjot K. Monga, Aaron Bell, Ajit Sood, Vanita Malhotra, Neena Sood, Vandana Midda, Dulabh K. Monga, Demetrius M. Kokkinakis, Satdarshan P.S. Monga, Aberrant Wnt/β-Catenin Signaling in Pancreatic Adenocarcinoma Neoplasia. ,vol. 8, pp. 279- 289 ,(2006) , 10.1593/NEO.05607
Oliver Stoeltzing, Wenbiao Liu, Niels Reinmuth, Fan Fan, Alexander A. Parikh, Corazon D. Bucana, Douglas B. Evans, Gregg L. Semenza, Lee M. Ellis, Regulation of Hypoxia-Inducible Factor-1α, Vascular Endothelial Growth Factor, and Angiogenesis by an Insulin-Like Growth Factor-I Receptor Autocrine Loop in Human Pancreatic Cancer American Journal of Pathology. ,vol. 163, pp. 1001- 1011 ,(2003) , 10.1016/S0002-9440(10)63460-8
Olivier Gires, Christoph A. Klein, Patrick A. Baeuerle, On the abundance of EpCAM on cancer stem cells Nature Reviews Cancer. ,vol. 9, pp. 143- 143 ,(2009) , 10.1038/NRC2499-C1
Michael F Clarke, John E Dick, Peter B Dirks, Connie J Eaves, Catriona HM Jamieson, D Leanne Jones, Jane Visvader, Irving L Weissman, Geoffrey M Wahl, None, Cancer stem cells--perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Research. ,vol. 66, pp. 9339- 9344 ,(2006) , 10.1158/0008-5472.CAN-06-3126
Yu-Jun Li, β-catenin up-regulates the expression of cyclinD1, c-myc and MMP-7 in human pancreatic cancer: Relationships with carcinogenesis and metastasis World Journal of Gastroenterology. ,vol. 11, pp. 2117- 2123 ,(2005) , 10.3748/WJG.V11.I14.2117
Patrick C. Hermann, Sonu Bhaskar, Michele Cioffi, Christopher Heeschen, Cancer stem cells in solid tumors. Seminars in Cancer Biology. ,vol. 20, pp. 77- 84 ,(2010) , 10.1016/J.SEMCANCER.2010.03.004
Michael P. Kim, Jason B. Fleming, Huamin Wang, James L. Abbruzzese, Woonyoung Choi, Scott Kopetz, David J. McConkey, Douglas B. Evans, Gary E. Gallick, ALDH Activity Selectively Defines an Enhanced Tumor-Initiating Cell Population Relative to CD133 Expression in Human Pancreatic Adenocarcinoma PLoS ONE. ,vol. 6, pp. e20636- ,(2011) , 10.1371/JOURNAL.PONE.0020636