3,3′-Diindolylmethane Induces G1 Arrest and Apoptosis in Human Acute T-Cell Lymphoblastic Leukemia Cells

Abstract

Certain bioactive food components, including indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) from cruciferous vegetables, have been shown to target cellular pathways regulating carcinogenesis. Previously, our laboratory showed that dietary I3C is an effective transplacental chemopreventive agent in a dibenzo[ def,p ]chrysene (DBC)-dependent model of murine T-cell lymphoblastic lymphoma. The primary objective of the present study was to extend our chemoprevention studies in mice to an analogous human neoplasm in cell culture. Therefore, we tested the hypothesis that I3C or DIM may be chemotherapeutic in human T-cell acute lymphoblastic leukemia (T-ALL) cells. Treatment of the T-ALL cell lines CCRF-CEM, CCRF-HSB2, SUP-T1 and Jurkat with DIM in vitro significantly reduced cell proliferation and viability at concentrations 8- to 25-fold lower than the parent compound I3C. DIM (7.5 µM) arrested CEM and HSB2 cells at the G 1 phase of the cell cycle and 15 µM DIM significantly increased the percentage of apoptotic cells in all T-ALL lines. In CEM cells, DIM reduced protein expression of cyclin dependent kinases 4 and 6 (CDK4, CDK6) and D-type cyclin 3 (CCND3); DIM also significantly altered expression of eight transcripts related to human apoptosis ( BCL2L10 , CD40LG , HRK , TNF , TNFRSF1A , TNFRSF25 , TNFSF8 , TRAF4 ). Similar anticancer effects of DIM were observed in vivo . Dietary exposure to 100 ppm DIM significantly decreased the rate of growth of human CEM xenografts in immunodeficient SCID mice, reduced final tumor size by 44% and increased the apoptotic index compared to control-fed mice. Taken together, our results demonstrate a potential for therapeutic application of DIM in T-ALL.

3,3'-Diindolylmethane Ameliorates Staphylococcal Enterotoxin B-Induced Acute Lung Injury through Alterations in the Expression of MicroRNA that Target Apoptosis and Cell-Cycle Arrest in Activated T Cells

“…DIM has been shown to have potent antiproliferative properties in a multitude of cancer cells lines, inducing apoptosis and/or cell-cycle disruption (Shorey et al, 2012;Weng et al, 2012a;Jin et al, 2015). In this current study, we determined the possibility that DIM may induce cell death in SEBactivated T cells.…”

1,1-Bis (3′-indolyl)-1-(p-substitutedphenyl)methane compounds inhibit lung cancer cell and tumor growth in a metastasis model

“…Studies have underscored the anticancer and/or antitumor activities of 3,3′-diindolylmethane (DIM), a metabolite of the naturally-occurring indole-3-carbinol (I3C) found in cruciferous vegetables such as broccoli (Chen et al, 2012; Shorey et al, 2012). The anticancer activity of DIM has been investigated in various cell lines including prostate, breast, and colon (Abdelbaqi et al, 2011; Chen et al, 2012; Lerner et al, 2012).…”

The Proliferation and Migration-Enhancing Effects of Vitronectin in SMMC 7721 Cells: A Pilot Study

“…In vitro studies indicate that I3C and DIM affect activation of carcinogens and initiation and progress of tumor via a variety of ways, inducing apoptosis in various tumor cells such as breast cancer, prostate cancer, endometrial cancer, colorectal cancer and leukemia cells etc. [18][19][20][21]. Previous studies by our group show that I3C and DIM can inhibit proliferation of poorly differentiated nasopharyngeal carcinoma cell line CNE1, human hepatoma cell lines HepG2 and SMMC 7721 cell as well as induce apoptosis of these types of cells [22] in a concentration-dependent manner and time-dependent manner.…”