Abstract | PURPOSE: EXPERIMENTAL DESIGN: The synthetic curcumin analogue dimethoxycurcumin was compared with curcumin for ability to inhibit proliferation and apoptosis of human HCT116 colon cancer cells in vitro by estimating the GI(50) and LC(50) values and detecting the extent of apoptosis by flow cytometry analysis of the cell cycle. Metabolic stability and/or identification of metabolites were evaluated by recently developed mass spectrometric approaches after incubation with mouse and human liver microsomes and cancer cells in vitro. Additionally, circulating levels of dimethoxycurcumin and curcumin were determined in mice following i.p. administration. RESULTS: CONCLUSIONS: Compared with curcumin, dimethoxycurcumin is (a) more stable in cultured cells, (b) more potent in the ability to kill cancer cells by apoptosis, (c) less extensively metabolized in microsomal systems, and (d) more stable in vivo. It is likely that the differential extent of apoptosis induced by curcumin and dimethoxycurcumin in vitro is associated with the metabolite profiling and/or the extent of stability.
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Authors | Constantin Tamvakopoulos, Konstantinos Dimas, Zacharias D Sofianos, Sophia Hatziantoniou, Zhiyong Han, Zhong-Li Liu, James H Wyche, Panayotis Pantazis |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 4
Pg. 1269-77
(Feb 15 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 17317839
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- dimethoxycurcumin
- Curcumin
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Topics |
- Animals
- Antineoplastic Agents
(metabolism, pharmacology)
- Apoptosis
(drug effects)
- Cell Growth Processes
(drug effects)
- Colonic Neoplasms
(drug therapy, metabolism, pathology)
- Curcumin
(analogs & derivatives, metabolism, pharmacology, toxicity)
- Drug Screening Assays, Antitumor
- Drug Stability
- Female
- Flow Cytometry
- HCT116 Cells
- Humans
- Male
- Mice
- Microsomes, Liver
(metabolism)
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