3,3'-Diindolylmethane increases serum interferon-γ levels in the K14-HPV16 transgenic mouse model for cervical cancer

• Published in: In vivo (Athens) Vol. 26; no. 2; p. 207
• Main Authors: Sepkovic, Daniel W, Raucci, Laura, Stein, Johann, Carlisle, Antoine D, Auborn, Karen, Ksieski, H Barbara, Nyirenda, Themba, Bradlow, H Leon
• Format: Journal Article
• Language: English
• Published: Greece 01.03.2012
• Subjects: Administration, Oral; Animals; Anticarcinogenic Agents - administration & dosage; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Carcinoma, Squamous Cell - blood; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - prevention & control; Cervical Intraepithelial Neoplasia - blood; Cervical Intraepithelial Neoplasia - genetics; Cervical Intraepithelial Neoplasia - pathology; Cervical Intraepithelial Neoplasia - prevention & control; Dose-Response Relationship, Drug; Epithelial Cells - metabolism; Estradiol - analogs & derivatives; Estradiol - blood; Estradiol - pharmacokinetics; Estradiol - toxicity; Female; Human papillomavirus 16 - genetics; Indoles - administration & dosage; Indoles - pharmacology; Indoles - therapeutic use; Interferon-gamma - blood; Keratin-14 - genetics; Mice; Mice, Transgenic; Neoplasms, Hormone-Dependent - blood; Neoplasms, Hormone-Dependent - genetics; Neoplasms, Hormone-Dependent - pathology; Neoplasms, Hormone-Dependent - prevention & control; Oncogene Proteins, Viral - biosynthesis; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - physiology; Papillomavirus E7 Proteins - biosynthesis; Papillomavirus E7 Proteins - genetics; Papillomavirus E7 Proteins - physiology; Promoter Regions, Genetic; Recombinant Fusion Proteins - biosynthesis; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - physiology; Repressor Proteins - biosynthesis; Repressor Proteins - genetics; Repressor Proteins - physiology; Transgenes; Uterine Cervical Neoplasms - blood; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - prevention & control
• ISSN: 1791-7549

While cervical cancer incidence and mortality rates have declined in the United States, this cancer represents a worldwide threat. Human papilloma viral infection causes cervical neoplasia (CIN). 3,3'-Diindolylmethane (DIM) prevents or inhibits the progression from cervical dysplasia to cancer. The aim of this study is to determine the most effective dose of DIM given continuously in food, that significantly increases serum interferon gamma levels (IFN-γ) in the K14-HPV16 transgenic mouse model for cervical cancer. Five doses of DIM in food were administered to the mouse model for 20 weeks. Serum Interferon gamma (IFN-γ) levels and estrogen metabolite levels were quantified. At 1000 ppm DIM, serum IFN-γ concentrations were significantly increased (p<0.0396). The estrogen metabolites were unchanged. IFN-γ concentrations in CIN free mice and the percentage of CIN free transgenic mice were well correlated (r=0.88). Significant increases in IFN-γ serum concentrations that correlate with the percentage of CIN free mice in each group indicate that 1000 ppm of DIM in food may be the most effective dose for future studies. These results may eventually lead to new and effective vaccination strategies in women already infected with the human papilloma virus.