Synthesis and antitumor properties of selenocoxib-1 against rat prostate adenocarcinoma cells

Int J Cancer. 2010 Jul 1;127(1):230-8. doi: 10.1002/ijc.25033.


Hormone refractory prostate cancer poses a huge problem and standard of care chemotherapy has not been very successful. We used a novel strategy to combine properties of 2 well-studied class of compounds (selenium and COX-2 inhibitor) and examined the resulting effectiveness against prostate cancer. Bearing in mind that sulfonamide moiety and pyrazole ring is important for the proapoptotic activity of Celecoxib, we synthesized a selenium derivative, Selenocoxib-1, by modifying Celecoxib at position 3 of the pyrazole ring. The PAIII cells derived from a metastatic prostate tumor that arose spontaneously in a Lobund-Wistar (LW) rat were used to examine the efficacy of Selenocoxib-1 in vitro. In addition, human metastatic prostate cancer cells, PC-3M, were tested for antitumor effect of Selenocoxib-1 in vitro. The IC(50) in PAIII and PC-3M cells for Selenocoxib-1 was about 5 microM, while for Celecoxib it was more than 20 microM. Selenocoxib-1 induced apoptosis in a dose-dependent manner in the PAIII cells. COX-2 expression in PAIII cells was downregulated by Celecoxib and Selenocoxib-1 at 20 and 5 microM, respectively; the COX-2 activity was, however, not affected by Selenocoxib-1. Following treatment with Selenocoxib-1, PAIII cells resulted in dose-dependent decrease in HIF-1alpha, p-AKT and Bcl-2 levels. A reduction in weights was observed in subcutaneous tumors produced by PAIII cells pretreated with Selenocoxib-1 as compared to Celecoxib in LW rats. Further, following 1 week Selenocoxib-1 treatment of PAIII tumors resulted in significant reduction of tumor weights. This study demonstrates that Selenocoxib-1 is more effective against prostate cancer than Celecoxib.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / pathology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Blotting, Western
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Organoselenium Compounds / pharmacology*
  • Prostatic Neoplasms / pathology*
  • Rats
  • Rats, Wistar
  • Selenium / blood
  • Sulfonamides / pharmacology*


  • Antineoplastic Agents
  • Organoselenium Compounds
  • Sulfonamides
  • selenocoxib-1
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Selenium