Cancer Chemoprevention by Curcumin and Structurally Related Beta-Diketones
MacDonald, Christopher James
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https://hdl.handle.net/2142/84985
Description
Title
Cancer Chemoprevention by Curcumin and Structurally Related Beta-Diketones
Author(s)
MacDonald, Christopher James
Issue Date
1999
Doctoral Committee Chair(s)
Singletary, Keith W.
Department of Study
Nutritional Sciences
Discipline
Nutritional Sciences
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Oncology
Language
eng
Abstract
Curcumin is a beta-diketone constituent of the spice turmeric that possesses anticarcinogenic properties in several animal models. However, the effectiveness of curcumin to act as an inhibitor of mammary carcinogenesis needs further attention. The present studies were conducted in order to evaluate curcumin, and structurally related compounds, to act as effective blocking agents toward the initiation stage of chemically induced carcinogenesis. We have shown that curcumin can inhibit tumorigenesis when administered intraperitoneally. After screening various compounds for their capacity to induce quinone-reductase (QR) activity in wild-type Hepa1c1c7 cells and a mutant subdone, curcumin and dibenzoylmethane were found to be most effective. However, when added to semipurified diets fed to female rats, dibenzoylmethane (1%), but not curcumin (1%), was effective in inhibiting in vivo mammary DMBA-DNA adduct formation. This inhibitory effect on mammary adduct formation was associated with a significant increase in liver activities of glutathione S-transferase, QR and 7-ethoxyresorufin-O-deethylase activities. Female rats provided diets supplemented with dibenzoylmethane at 0.1, 0.5 and 1.0% for 14 days prior to dosing with DMBA exhibited a significant decrease in mammary tumor development, compared with controls, while the curcumin supplemented diet (1%) had no effect. DBM was also an effective inhibitor of BP-DNA adduct formation in the non-neoplastic, human mammary epithelial cell line, MCF-10F, at concentrations of 0.5, 1.0 and 2.0 muM (supplemented in DME/F12 media). This was associated with a significant induction of QR activity and an increase in QR protein levels as measured by western analysis. Finally, when compared to sulforaphane and resveratrol, DBM and sulforaphane showed an equal capacity to inhibit BP-DNA adduct formation, while all three compounds we able to inhibit 1,6-DNP-DNA to a similar magnitude. DBM, therefore, has promise as a chemopreventative agent.
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