Chemopreventive efficacy of stampidine in a murine breast cancer model

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.

KEYWORDS:

• Stampidine
• paclitaxel
• apoptosis
• breast cancer
• mice

Author contributions

KS, FMU, and SQ were involved in the conception and design; CO, MT, and KS performed the experiments; CO, IHO, MT, UK, and BE were involved in analysis and interpretation of the data; SQ and CO performed statistical analyses; TKS and UK drafted the manuscript; KS and FMU wrote and revised the paper. All the authors read and approved the final version of the manuscript. All authors agree to be accountable for all aspects of the work.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The project described was supported in part by DHHS grants P30 CA014089, U01-CA-151837, R01CA-154471, R21-CA-164098 (F.M.U) from the National Cancer Institute, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. KS was supported in part by the research fund of the Turkish Academy of Sciences, Turkey. F.M.U is the laureate of the 2018 TUBA Academy Prize in Health and Life Sciences of the Turkish Academy of Sciences, Turkey. The funders had no role in the paper design, data collection, data analysis, interpretation, writing of the paper.