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Author Notes:

To whom correspondence should be addressed: Mamoru Shoji: Tel: (404) 727-3457. Fax: (404) 778-5016. mshoji@emory.edu.

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Research Funding:

Grant Support. This research was supported by the National Cancer Institute award 5 P50 CA128613 SPORE in Head and Neck Cancer (SZ, TWM, HZ, XL, GC, HF, FRK, DMS, JPS, MS), the National Institutes of Health (NIH) grant R21CA82995-01A1, the U.S. Department of Defense, Division of U.S. Army DAMD17-00-1-0241 (MS), and the Emory Institute for Drug Discovery (TWM, AM, RBH, DC, RFA, GRP, TJE, AS, JPS).

Keywords:

  • synthetic curcumin analog
  • EF31
  • pharmacokinetic and toxicologic studies
  • NF-kB p65 phosphorylation

Synthetic curcumin analog EF31 inhibits the growth of head and neck squamous cell carcinoma xenografts

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Journal Title:

Integrative Biology

Volume:

Volume 4, Number 6

Publisher:

, Pages 633-640

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Objectives are to examine the efficacy of new synthetic curcumin analogs EF31 in head and neck squamous cell carcinoma in vitro and in vivo, and study their pharmacokinetic and toxicologic effects in vivo. The synthesis of EF31 was described for the first time. Solubility of EF24, EF31 was compared using nephelometric analysis. Human head and neck squamous cell carcinoma Tu212 xenograft tumors were established in athymic nude mice and treated with EF31 i.p. once daily five days a week for about 5 – 6 weeks. The long term effect of EF31 on the NF-κB signaling system in the tumors was examined by Western blot analysis. EF31 at 25 mg/kg, i.p. inhibited tumor growth almost completely. Solubility of EF24 and EF31 are <10, 13 μg/mL or <32, 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, it revealed a linear increase of Cmax. EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analogs EF31 is efficacious in inhibiting the growth of Tu212 xenograft tumors and may be useful for treating head and neck squamous cell carcinoma. The long term EF31 treatment inhibited NF-kB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.

Copyright information:

© The Royal Society of Chemistry 2012

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