3,3'-Diindolylmethane and its derivatives: nature-inspired strategies tackling drug resistant tumors by regulation of signal transduction, transcription factors and microRNAs.

Bernhard Biersack

doi:10.20517/cdr.2020.53

Abstract

Indoles of cruciferous vegetables are promising anti-tumor agents. Studies with indole-3-carbinol and its dimeric product, 3,3’-diindolylmethane (DIM), suggest that these compounds have the ability to deregulate multiple cellular signaling pathways that are essential for tumor growth and spread. These natural compounds are also effective modulators of transcription factors and non-coding RNAs. These effects explain their ability to inhibit tumor spread and to overcome drug resistance. In this work, pertinent literature on the effects of DIM and its synthetic derivatives on resistant tumors and resistance mechanisms in tumors is highlighted.

Highlights

Cancer is one of the most serious human health concerns
The general anticancer properties of DIM based on mechanisms such as apoptosis induction, blocking of NF-κB, Akt and Wnt signaling, effects on PI3K/Akt/mTOR signaling and aryl hydrocarbon receptor (Ahr) signaling as well as antioxidant properties have already been reviewed[7,11,20,21]
Another study of BR-DIM in prostatectomy patients with prostate cancer showed that BR-DIM was well tolerated, and DIM was detected in prostate biopsies and blood plasma

Summary

Introduction

Cancer is one of the most serious human health concerns. The current treatments of cancer comprise of surgery, radiation therapy, chemotherapy with classical cytotoxic drugs and/or targeted drugs (e.g., protein kinase inhibitors), endocrine therapy, and immunotherapy[1,2,3]. An Ahr-mediated induction of miR-212/132 cluster expression was promoted by DIM in the drug-resistant breast cancer models T47D and MDA-MB-231, which led to downregulation of the pro-metastatic SRTY-related HMG-box 4 (Sox4) protein. DIM inhibited cancer cell invasion by suppression of metastasis-associated protein 2 (MTA2), NF-κB, interleukin 1 receptor-associated kinase 1 (IRAK1), and epidermal growth factor receptor (EGFR) based on upregulation of miR-146a[36].

Results

Conclusion