May 27, 2005
Celebrex and Akt: Blocking the Pathway of Cancer Cell Survival
Erika Reynoso
California State University, Los Angeles
MARC U*STAR Scholar
ABSTRACT:
The Akt pathway is a signal transduction pathway involved
in cellular growth, survival and movement. Akt controls activation
of downstream substrates through phosphorylation; its activation
has been found to inhibit cancer cell death and to promote formation
and growth of cancer cells. Celecoxib, commercially known as Celebrex,
is a non-steroidal anti-inflammatory drug that has been found
to block this pathway through inhibition of an upstream kinase,
resulting in cancer cell cycle arrest and apoptosis. However,
celecoxib has drawbacks, including unfavorable pharmacokinetics
and weak inhibition of the Akt pathway. Structure-based optimization
of celecoxib has led to the formulation of celecoxib derivatives,
of which, OSU-03012 has been shown to be a better inhibitor of
the Akt pathway in prostate cancer cell lines. Using timed dose-response
experiments with various cancer cell lines, our group has sought
to characterize the bioactivity of OSU-03012 in order to evaluate
its potential as a novel cancer chemotherapeutic.
and
Preparation of Building Blocks for Tetraamino-Adamantane
Dendrimers
Gina Ramirez
California State University, Los Angeles
MBRS-RISE Undergraduate Student