Cancer Chemoprevention by Curcumin and Structurally Related Beta-Diketones

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Nutritional Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• MacDonald, Christopher James

Contributors dc:contributor

• Singletary, Keith W.

• Health Sciences, Oncology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9953086

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84985