Abstract | BACKGROUND: METHODS: Cell proliferation was assessed by the MTT assay. Cell apoptosis and mitochondria membrane potential were evaluated by high content screening analysis. Intracellular polyamine content was detected by HPLC. Protein expression was detected by western blot analysis. RESULTS: The co-treatment with celecoxib enhanced NPC-16-induced apoptosis in HCT116 (COX-2 no expression), HT29 (COX-2 higher expression) and Caco-2 (COX-2 higher expression) colorectal cancer cells, which was mediated by the elevated NPC-16 uptake via the effect of celecoxib on polyamine metabolism, including the up-regulated spermidine/spermine N(1)-acetyltransferase (SSAT) activity and reduced intracellular polyamine levels. The presence of celecoxib does not result in obviously different effect on the NPC-16-triggered apoptosis in diverse COX-2 expressed colorectal cell lines, suggesting that COX-2 was not one vital factor in the apoptotic mechanism. Furthermore, this synergistic apoptosis was involved in the PKB/AKT signal pathway, Bcl-2 and caspase family members. Z-VAD-FMK, a cell permeable pan caspase inhibitor, almost completely inhibited celecoxib and NPC-16 co-induced apoptosis, indicating that this apoptosis was caspase dependent. CONCLUSIONS:
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Authors | Song-qiang Xie, Ya-hong Zhang, Qian Li, Jian-hong Wang, Jing-hua Li, Jin Zhao, Chao-jie Wang |
Journal | International journal of colorectal disease
(Int J Colorectal Dis)
Vol. 27
Issue 7
Pg. 861-8
(Jul 2012)
ISSN: 1432-1262 [Electronic] Germany |
PMID | 22159752
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acid Chloromethyl Ketones
- NPC 16
- Naphthalimides
- Polyamines
- Proto-Oncogene Proteins c-bcl-2
- Pyrazoles
- Sulfonamides
- benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
- Cytochromes c
- Cyclooxygenase 2
- PTGS2 protein, human
- Acetyltransferases
- diamine N-acetyltransferase
- Proto-Oncogene Proteins c-akt
- Caspases
- Celecoxib
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Topics |
- Acetyltransferases
(metabolism)
- Amino Acid Chloromethyl Ketones
(pharmacology)
- Apoptosis
(drug effects)
- Caspases
(metabolism)
- Celecoxib
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Colorectal Neoplasms
(drug therapy, enzymology, pathology)
- Cyclooxygenase 2
(metabolism)
- Cytochromes c
(metabolism)
- Drug Synergism
- Enzyme Activation
(drug effects)
- Humans
- Membrane Potential, Mitochondrial
(drug effects)
- Naphthalimides
(chemistry, pharmacology, therapeutic use)
- Polyamines
(metabolism, pharmacology, therapeutic use)
- Proto-Oncogene Proteins c-akt
(metabolism)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Pyrazoles
(pharmacology, therapeutic use)
- Sulfonamides
(pharmacology, therapeutic use)
- Up-Regulation
(drug effects)
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