The Possible Chemosensitizing Effect of Different Doses of Indol-3-Carbinol on Transplantable Tumor Model Treated with Doxorubicin

Abstract

Background: Ehrlich carcinoma is a transplantable tumor model used frequently in cancer studies. Doxorubicin (DOX) is one of the anthracyclines that is frequently used in treatment of various types of malignancies including breast, prostate and lung cancer. Indole-3-carbinol (I3C) is a phytochemical that was suggested to have potent anti-tumor and chemosensitizing effects. Objective: To detect the possible chemosensitizing effects of different doses of I3C on solid Ehrlich carcinoma (SEC) treated with DOX in mice. Materials and methods: One hundred and forty mice were divided into seven equal groups as follows: Control untreated group, solid Ehrlich carcinoma (SEC), SEC + DOX, SEC + I3C 1000 ppm, SEC + I3C 2000 ppm, SEC + DOX + I3C 1000 ppm and SEC + DOX + I3C 2000 ppm. Tumor volume, survival rate, tissue glutathione reductase (GR), tissue glutathione peroxidase (GPx), tissue tumor necrosis factor alpha (TNF-α) and tissue interleukin-6 (IL-6) were determined. Parts of the tumor were subjected to histopathological and immunohistochemical examination. Results: DOX and/or I3C produced significant increase in the survival rate, tissue GPx and tissue GR with significant decrease in tumor volume, tissue TNF-α and tissue IL-6 compared to SEC group. Moreover, they improved the histopathological changes with significant increase in tissue caspase-3 activity and p53 compared to SEC group. These effects were significant in DOX/I3C combination groups compared to the use of each of these drugs alone. Conclusion: I3C-in a dose dependent manner - had a chemosensitizing effect against transplantable tumor model treated with DOX in mice and this might represent an adjuvant to the traditional drugs used in cancer chemotherapy.