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3,3′-Diindolylmethane Induces Apoptosis in Human Cancer Cells

https://doi.org/10.1006/bbrc.1996.1631Get rights and content

Abstract

3,3′-Diindolylmethane is a dimer of indole-3-carbinol formed bothin vivoandin vitro.In this study, human cancer cells MCF-7 (with wild-type p53), T47-D (mutant p53), and Saos-2 (deficient in p53 gene), were used to examine the anticancer activities of 3,3′-diindolylmethane. The dose-dependent growth inhibitory effect was found in all these cell lines. Exposure of the cells to 50 μM solution of 3,3′-diindolylmethane for 48 h, apoptosis (programmed cell death) was evidenced by the characteristic morphology of cell nuclei under fluorescence microscope and the DNA “ladder” in agarose gel electrophoresis. The percentage of apoptotic cells in each cell line was found to be 12% for MCF-7, 14% for T47D and 13% for Saos2 cells. Exposure of MCF-7 cells to 100 μM 3,3′-diindolylmethane for 24 h, 19% of apoptotic cells were detected by flow cytometry analysis. The lowest dose required for induction of apoptosis in MCF-7 cells was found to be 10 μM after 72 h incubation. Western blot showed that wild-type p53 protein was unchanged after MCF-7 cells had been exposed to 50 μM 3,3′-diindolylmethane for 8 h. This study provides evidences that 3,3′-diindolylmethane induces apoptosis in human cancer cells and that the induction of apoptosis is independent of p53 pathway.

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    Citation Excerpt :

    Bis(indolyl)methanes (BIMs) contain two indole units in a molecule, which is a particular feature of the bioactive metabolites of terrestrial and marine origins [2]. BIMs are active substances that promote beneficial estrogen metabolism and induce apoptosis in human cancer cells [3], in addition to their wide range of biological, industrial, and synthetic applications [4]. Therefore, significant efforts have been made to synthesize BIMs [5].

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To whom correspondence should be addressed, at Department of Biochemistry, The Lady Davis Carmel Medical Center, Haifa 34362, Israel. Fax: 00972-4-8343023. E-mail: [email protected].

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