Abstract |
Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) is frequently detected in osteosarcoma, and hence, may serve as a therapeutic target. In order to target STAT3, we tested two new STAT3 inhibitors, LLL12 and FLLL32. LLL12 and FLLL32 inhibit STAT3 phosphorylation and STAT3 downstream targets. LLL12 and FLLL32 also inhibit IL-6 induced STAT3 phosphorylation. The inhibition of STAT3 by LLL12 and FLLL32 resulted in the induction of apoptosis, reduction of plating efficiency, and migration in osteosarcoma cells. Furthermore, LLL12 and FLLL32 inhibited SJSA osteosarcoma cells and OS-33 tumor growth in murine xenografts. These results provide evidence that constitutive STAT3 signaling is required for osteosarcoma survival and migration in vitro and tumor growth in vivo. Blocking persistent STAT3 signaling by LLL12 and FLLL32 may be a novel therapeutic approach for osteosarcoma.
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Authors | Grace-Ifeyinwa Onimoe, Aiguo Liu, Li Lin, Chang-Ching Wei, Eric B Schwartz, Deepak Bhasin, Chenglong Li, James R Fuchs, Pui-kai Li, Peter Houghton, Amanda Termuhlen, Thomas Gross, Jiayuh Lin |
Journal | Investigational new drugs
(Invest New Drugs)
Vol. 30
Issue 3
Pg. 916-26
(Jun 2012)
ISSN: 1573-0646 [Electronic] United States |
PMID | 21340507
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anthraquinones
- Antineoplastic Agents
- FLLL 32
- Interleukin-6
- LLL12 compound
- STAT3 Transcription Factor
- STAT3 protein, human
- Sulfonamides
- Curcumin
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Topics |
- Animals
- Anthraquinones
(pharmacology, therapeutic use)
- Antineoplastic Agents
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Bone Neoplasms
(drug therapy, metabolism, pathology)
- Cell Line
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Curcumin
(analogs & derivatives, pharmacology, therapeutic use)
- Female
- Humans
- Interleukin-6
(pharmacology)
- Mice
- Mice, Nude
- Osteosarcoma
(drug therapy, metabolism, pathology)
- Phosphorylation
(drug effects)
- STAT3 Transcription Factor
(antagonists & inhibitors, metabolism)
- Sulfonamides
(pharmacology, therapeutic use)
- Tumor Burden
(drug effects)
- Xenograft Model Antitumor Assays
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