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Open Access Highly Accessed Research article

Biologic activity of the novel small molecule STAT3 inhibitor LLL12 against canine osteosarcoma cell lines

Jason I Couto1, Misty D Bear1, Jiayuh Lin23, Michael Pennel5, Samuel K Kulp6, William C Kisseberth4 and Cheryl A London1*

Author Affiliations

1 Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA

2 Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH, 43205, USA

3 Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA

4 Department of Veterinary Clinical Sciences, The Ohio State University, Columbus, OH, 43210, USA

5 College of Public Health, The Ohio State University, Columbus, OH, 43210, USA

6 Department of Medicinal Chemistry, College of Pharmacy, The Ohio State University, Columbus, OH, 43210, USA

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BMC Veterinary Research 2012, 8:244  doi:10.1186/1746-6148-8-244

Published: 17 December 2012

Abstract

Background

STAT3 [1] has been shown to be dysregulated in nearly every major cancer, including osteosarcoma (OS). Constitutive activation of STAT3, via aberrant phosphorylation, leads to proliferation, cell survival and resistance to apoptosis. The present study sought to characterize the biologic activity of a novel allosteric STAT3 inhibitor, LLL12, in canine OS cell lines.

Results

We evaluated the effects of LLL12 treatment on 4 canine OS cell lines and found that LLL12 inhibited proliferation, induced apoptosis, reduced STAT3 phosphorylation, and decreased the expression of several transcriptional targets of STAT3 in these cells. Lastly, LLL12 exhibited synergistic anti-proliferative activity with the chemotherapeutic doxorubicin in the OS lines.

Conclusion

LLL12 exhibits biologic activity against canine OS cell lines through inhibition of STAT3 related cellular functions supporting its potential use as a novel therapy for OS.

Keywords:
STAT3; Osteosarcoma; Canine