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Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wntβ-Catenin Pathways
Joint Authors
Fontana, Joseph A.
Das, Jayanta K.
Dawson, Marcia I.
Murshed, Farhan
Xia, Zebin
Farhana, Lulu
Hatfield, James
Hadden, Timothy J.
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-04-05
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Pancreatic carcinoma has a dismal prognosis as it often presents as 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 and apoptosis induction in PANC-1, Capan-2, and MiaPaCa-2 pancreatic cancer cell lines.
In addition, AHP3 and 3-Cl-AHPC inhibited growth and induced apoptosis in spheres derived from the CD44+/CD24+ (CD133+/EpCAM+) stem-like cell population isolated from the pancreatic cancer cell lines.
3-Cl-AHPC-induced apoptosis was preceded by decreasing expression of IGF-1R, cyclin D1, β-catenin, and activated Notch-1 in the pancreatic cancer cell lines.
Decreased IGF-1R expression inhibited PANC-1 proliferation, enhanced 3-Cl-AHPC-mediated apoptosis, and significantly decreased sphere formation.
3-Cl-AHPC inhibited the Wnt/β-catenin pathway as indicated by decreased β-catenin nuclear localization and inhibited Wnt/β-catenin activation of transcription factor TCF/LEF.
Knockdown of β-catenin using sh-RNA also induced apoptosis and inhibited growth in pancreatic cancer cells.
Thus, 3-Cl-AHPC and AHP3 induce apoptosis in pancreatic cancer cells and cancer stem-like cells and may serve as an important potential therapeutic agent in the treatment of pancreatic cancer.
American Psychological Association (APA)
Farhana, Lulu& Dawson, Marcia I.& Das, Jayanta K.& Murshed, Farhan& Xia, Zebin& Hadden, Timothy J.…[et al.]. 2012. Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wntβ-Catenin Pathways. Journal of Oncology،Vol. 2012, no. 2012, pp.1-14.
https://search.emarefa.net/detail/BIM-498877
Modern Language Association (MLA)
Farhana, Lulu…[et al.]. Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wntβ-Catenin Pathways. Journal of Oncology No. 2012 (2012), pp.1-14.
https://search.emarefa.net/detail/BIM-498877
American Medical Association (AMA)
Farhana, Lulu& Dawson, Marcia I.& Das, Jayanta K.& Murshed, Farhan& Xia, Zebin& Hadden, Timothy J.…[et al.]. Adamantyl Retinoid-Related Molecules Induce Apoptosis in Pancreatic Cancer Cells by Inhibiting IGF-1R and Wntβ-Catenin Pathways. Journal of Oncology. 2012. Vol. 2012, no. 2012, pp.1-14.
https://search.emarefa.net/detail/BIM-498877
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-498877