AACR meeting abstract: Interaction between effects of vitamin D3 and NSAIDs in prostate and colon epithelial cells

Abstract Number: 3287

Presentation Title:

Interaction between effects of vitamin D3 and nonsteroidal
anti-inflammatory drugs in prostate and colon epithelial cells.
Presentation Start/End Time:

Monday, Apr 16, 2007, 1:00 PM - 5:00 PM
Location:

Exhibit Hall, Los Angeles Convention Center
Poster Section:

30
Poster Board Number:

19
Author Block:

Karel Soucek, Eva Lincova, Andrea Starsichova, Jirina Hofmanova, Alois
Kozubik. Institute of Biophysics, Brno, Czech Republic

Colon and prostate cancer are leading cause of cancer death in the
Western world. Anti-tumorigenic effects of vitamin D3 and nonsteroidal
anti-inflammatory drugs (NSAIDs) are well established in several types
of cancer disease. Interestingly it was shown that interaction between
effects of NSAIDs and vitamin D3 might exist. However, mechanisms
driving these processes are not known in all details. Finding the
molecular mechanisms associated with effects of NSAIDs and vitamin D3
in prostate and colon cancer is an important endeavor, and potentially
will lead to novel treatment strategies. It has been shown that some
effects of NSAIDs are independent on inhibition of activity of
cyclooxygenases. Induction of GDF-15 (PTGFb/NAG-1/MIC-1), gene from
transforming growth factor-b superfamily is associated with
pro-apoptotic and anti-tumorigenic effects of some NSAIDs.
In our study, we compared effects of selected NSAIDs in combination
with vitamin D3 on induction of GDF-15 protein in several cancer and
non-cancerous prostate and colon epithelial cell lines. We found
significant differences in response to treatment by NSAIDs in
combination with vitamin D3 and induction of GDF-15 protein between
individual cell lines. Increased induction of expression of GDF-15
protein after the treatment by NSAIDs and vitamin D3 was observed only
in cell lines with functional p53 protein. This observation correlates
with inhibition of proliferation and induction of cell cycle arrest.
Our observation showed importance of p53 status in sensitivity to
anti-proliferative effects of NSAIDs in combination with vitamin D3.
Supported by Grant Agency of the Czech Republic 204/07/0834,
310/07/0961, and IGA AVCR 1QS500040507.


--
Matti Narkia
.

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