Kazim Sahin1, Cemal Orhan1, Ibrahim Hanifi Ozercan2, Mehmet Tuzcu3, Birsen Elibol4, Taha Koray Sahin5, Ulkan Kilic6, Sanjive Qazi7,8,9, Fatih Mehmet Uckun7,8. 1. Department of Animal Nutrition, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey. 2. Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey. 3. Department of Molecular Biology, Faculty of Science, Firat University, Elazig, Turkey. 4. Department of Medical Biology, University of Bezmialem, School of Medicine, Istanbul, Turkey. 5. Department of Internal Medicine, University of Hacettepe School of Medicine, Ankara, Turkey. 6. Department of Medical Biology, University of Health Sciences, School of Medicine, Istanbul, Turkey. 7. Division of Hematology-Oncology, Department of Pediatrics, Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine (USC KSOM), Los Angeles, CA, USA. 8. Department of Immuno-Oncology, Ares Pharmaceuticals, St. Paul, MN, USA. 9. Gustavus Adolphus College, St. Peter, MN, USA.
Abstract
Background: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murine breast cancer model. Methods: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks. Results: Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2. Conclusion: Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.
Background: The purpose of the present study was to examine the chemopreventive effect of stampidine, an aryl phosphate derivative of stavudine, in side by side comparison with the standard anti-breast cancer drug paclitaxel in the well-established 7,12-dimethylbenz(a)anthracene (DMBA)-induced murinebreast cancer model. Methods: Groups of 20 female mice were challenged with the DMBA. DMBA-challenged mice were assigned to various chemoprevention treatments, including stampidine, paclitaxel, and stampidine plus paclitaxel according to the same treatment schedules for 25 weeks. Results:Stampidine resulted in substantially reduced numbers of tumors, tumor weight as well as tumor size in DMBA-treated mice. Stampidine was as effective as paclitaxel in the model and their combination exhibited greater chemopreventive activity, as measured by reduced tumor incidence and improved tumor-free survival as well as overall survival of DMBA-treated mice. The length of time for the initial tumor to appear in DMBA-challenged mice treated with stampidine was longer than that of mice treated DMBA-challenged control mice. Tumors from mice treated with stampidine or stampidine plus paclitaxel displayed unique changes of a signature protein cassette comprised BRCA1, p21, Bax, and Bcl-2. Conclusion:Stampidine has potent chemopreventive activity and is as effective as the standard chemotherapy drug paclitaxel in the chemical carcinogenesis.
Entities:
Keywords:
Stampidine; apoptosis; breast cancer; mice; paclitaxel
Authors: Prasanna K Santhekadur; Devaraja Rajasekaran; Ayesha Siddiq; Rachel Gredler; Dong Chen; Scott E Schaus; Ulla Hansen; Paul B Fisher; Devanand Sarkar Journal: Am J Cancer Res Date: 2012-04-21 Impact factor: 6.166