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

Abstract

Objectives are to examine the efficacy, pharmacokinetics, and toxicology of a synthetic curcumin analog EF31 in head and neck squamous cell carcinoma. The synthesis of EF31 was described for the first time. Solubility of EF24 and 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(-1), i.p. inhibited tumor growth almost completely. Solubilities of EF24 and EF31 are <10 and 13 μg mL(-1) or <32 and 47 μM, respectively. The serum chemistry profiles of treated mice were within the limits of normal, they revealed a linear increase of C(max). EF31 decreased the level of phosphorylation of NF-κB p65. In conclusion, the novel synthetic curcumin analog 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-κB p65 phosphorylation in xenografts, implicating downregulation of cancer promoting transcription factors such as angiogenesis and metastasis.

• Authors: Shijun Zhu, Terry W Moore, Xiaoqian Lin, Nao Morii, Alessandra Mancini, Randy B Howard, Deborah Culver, Richard F Arrendale, Prabhakar Reddy, Taylor J Evers, Hongzheng Zhang, Gabriel Sica, Zhuo G Chen, Aiming Sun, Haian Fu, Fadlo R Khuri, Dong M Shin, James P Snyder, Mamoru Shoji
• Journal: Integrative biology : quantitative biosciences from nano to macro (Integr Biol (Camb)) Vol. 4 Issue 6 Pg. 633-40 (Jun 2012) ISSN: 1757-9708 [Electronic] England
• PMID: 22532032 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 3,5-bis(2-pyridinylmethylidene)-4-piperidone
• Piperidones
• Transcription Factor RelA
• Curcumin

Topics

• Animals
• Blotting, Western
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Cell Survival (drug effects)
• Curcumin (analogs & derivatives, chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Female
• Head and Neck Neoplasms (drug therapy, metabolism, pathology)
• Humans
• Immunohistochemistry
• Male
• Mice
• Mice, Nude
• Phosphorylation (drug effects)
• Piperidones (chemical synthesis, chemistry, pharmacokinetics, pharmacology)
• Random Allocation
• Signal Transduction (drug effects)
• Solubility
• Specific Pathogen-Free Organisms
• Transcription Factor RelA (metabolism)
• Xenograft Model Antitumor Assays