This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jing, N. Articles by Tweardy, D. J. Search for Related Content PubMed PubMed Citation Articles by Jing, N. Articles by Tweardy, D. J.

Department of ¹ Medicine and ² Cancer Center, Baylor College of Medicine; ³ Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas; and ⁴ Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, China

Requests for reprints: Naijie Jing, Department of Medicine and Cancer Center, Baylor College of Medicine, One Baylor Plaza, N520, Houston, TX 77030. Phone: 713-798-3685; Fax: 713-798-8948. E-mail: njing{at}bcm.tmc.edu

Signal transducer and activator of transcription 3 (Stat3) is a critical mediator of oncogenic signaling activated frequently in many types of human cancer where it contributes to tumor cell growth and resistance to apoptosis. Stat3 has been proposed as a promising target for anticancer drug discovery. Recently, we developed a series of G-quartet oligodeoxynucleotides (GQ-ODN) as novel and potent Stat3 inhibitors, which significantly suppressed the growth of prostate and breast tumors in nude mice. In the present study, we showed that GQ-ODN specifically inhibited DNA-binding activity of Stat3 as opposed to Stat1. Computer-based docking analysis revealed that GQ-ODN predominantly interacts with the SH2 domains of Stat3 homodimers to destabilize dimer formation and disrupt DNA-binding activity. We employed five regimens in the treatment of nude mice with tumors of head and neck squamous cell carcinoma (HNSCC): placebo, paclitaxel, GQ-ODN T40214, GQ-ODN T40231, and T40214 plus paclitaxel. The mean size of HNSCC tumors over 21 days only increased by 1.7-fold in T40214-treated mice and actually decreased by 35% in T40214 plus paclitaxel–treated mice whereas the mean size of HNSCC tumors increased 9.4-fold in placebo-treated mice in the same period. These findings show that GQ-ODN has potent activity against HNSCC tumor xenografts alone and in combination with paclitaxel. [Mol Cancer Ther 2006;5(2):279–86]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁵ Q. Zhu and N. Jing, unpublished data.

Received 8/ 3/05; revised 10/13/05; accepted 11/21/05.

This article has been cited by other articles:

				A. Dagvadorj, R. A. Kirken, B. Leiby, J. Karras, and M. T. Nevalainen Transcription Factor Signal Transducer and Activator of Transcription 5 Promotes Growth of Human Prostate Cancer Cells In vivo Clin. Cancer Res., March 1, 2008; 14(5): 1317 - 1324. [Abstract] [Full Text] [PDF]

				H. Qi, C.-P. Lin, X. Fu, L. M. Wood, A. A. Liu, Y.-C. Tsai, Y. Chen, C. M. Barbieri, D. S. Pilch, and L. F. Liu G-Quadruplexes Induce Apoptosis in Tumor Cells Cancer Res., December 15, 2006; 66(24): 11808 - 11816. [Abstract] [Full Text] [PDF]

				B. B. AGGARWAL, G. SETHI, K. S. AHN, S. K. SANDUR, M. K. PANDEY, A. B. KUNNUMAKKARA, B. SUNG, and H. ICHIKAWA Targeting Signal-Transducer-and-Activator-of-Transcription-3 for Prevention and Therapy of Cancer: Modern Target but Ancient Solution Ann. N.Y. Acad. Sci., December 1, 2006; 1091(1): 151 - 169. [Abstract] [Full Text] [PDF]

				S. Burge, G. N. Parkinson, P. Hazel, A. K. Todd, and S. Neidle Quadruplex DNA: sequence, topology and structure Nucleic Acids Res., November 14, 2006; 34(19): 5402 - 5415. [Abstract] [Full Text] [PDF]