Abstract
Indole compounds, found in cruciferous vegetables, are potent anti-cancer agents. Studies with indole-3-carbinol (I3C) and its dimeric product, 3,3'-diindolylmethane (DIM) suggest that these compounds have the ability to deregulate multiple cellular signaling pathways, including PI3K/Akt/mTOR signaling pathway. These natural compounds are also effective modulators of downstream transcription factor NF-κB signaling which might help explain their ability to inhibit invasion and angiogenesis, and the reversal of epithelial-to-mesenchymal transition (EMT) phenotype and drug resistance. Signaling through PI3K/Akt/mTOR and NF-κB pathway is increasingly being realized to play important role in EMT through the regulation of novel miRNAs which further validates the importance of this signaling network and its regulations by indole compounds. Here we will review the available literature on the modulation of PI3K/Akt/mTOR/NF-κB signaling by both parental I3C and DIM, as well as their analogs/derivatives, in an attempt to catalog their anticancer activity.
Keywords: Indole compounds, PI3K, cancer therapy, NF-κB, Glucosinolates.
Anti-Cancer Agents in Medicinal Chemistry
Title:Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy
Volume: 13 Issue: 7
Author(s): Aamir Ahmad, Bernhard Biersack, Yiwei Li, Dejuan Kong, Bin Bao, Rainer Schobert, Subhash B. Padhye and Fazlul H. Sarkar
Affiliation:
Keywords: Indole compounds, PI3K, cancer therapy, NF-κB, Glucosinolates.
Abstract: Indole compounds, found in cruciferous vegetables, are potent anti-cancer agents. Studies with indole-3-carbinol (I3C) and its dimeric product, 3,3'-diindolylmethane (DIM) suggest that these compounds have the ability to deregulate multiple cellular signaling pathways, including PI3K/Akt/mTOR signaling pathway. These natural compounds are also effective modulators of downstream transcription factor NF-κB signaling which might help explain their ability to inhibit invasion and angiogenesis, and the reversal of epithelial-to-mesenchymal transition (EMT) phenotype and drug resistance. Signaling through PI3K/Akt/mTOR and NF-κB pathway is increasingly being realized to play important role in EMT through the regulation of novel miRNAs which further validates the importance of this signaling network and its regulations by indole compounds. Here we will review the available literature on the modulation of PI3K/Akt/mTOR/NF-κB signaling by both parental I3C and DIM, as well as their analogs/derivatives, in an attempt to catalog their anticancer activity.
Export Options
About this article
Cite this article as:
Ahmad Aamir, Biersack Bernhard, Li Yiwei, Kong Dejuan, Bao Bin, Schobert Rainer, Padhye B. Subhash and Sarkar H. Fazlul, Targeted Regulation of PI3K/Akt/mTOR/NF-κB Signaling by Indole Compounds and their Derivatives: Mechanistic Details and Biological Implications for Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (7) . https://dx.doi.org/10.2174/18715206113139990078
DOI https://dx.doi.org/10.2174/18715206113139990078 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Relationships of Beta2- and Beta3--Adrenoceptor Polymorphisms with Obesity, Hypertension and Metabolic Syndrome
Current Hypertension Reviews Effects of Hyperlipidemia and Cardiovascular Diseases on Proliferation, Differentiation and Homing of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Use of Analogs of Peptide Hormones Conjugated to Cytotoxic Radicals for Chemotherapy Targeted to Receptors on Tumors
Current Drug Delivery Retinoids in Clinical Use
Medicinal Chemistry Antidotal Effects of Curcumin Against Agents-Induced Cardiovascular Toxicity
Cardiovascular & Hematological Disorders-Drug Targets Biological Activity In Vitro of Side-Chain Modified Analogues of Calcitriol
Current Pharmaceutical Design Microgravity Alters Cancer Growth and Progression
Current Cancer Drug Targets Recent Developments in CE-MS Based Metabolomics
Current Analytical Chemistry Selective Inhibitors of Zinc-Dependent Histone Deacetylases. Therapeutic Targets Relevant to Cancer
Current Pharmaceutical Design Recent Patents on Novel P2X7 Receptor Antagonists and their Potential for Reducing Central Nervous System Inflammation
Recent Patents on CNS Drug Discovery (Discontinued) The Use of Cytokines and Chemokines in the Cancer Immunotherapy
Recent Patents on Anti-Cancer Drug Discovery Non-Vitamin K Oral Anticoagulants (NOACs) A Review of Clinical Management and Laboratory Issues
Current Vascular Pharmacology Look Into My Onco-forest - Review of Plant Natural Products with Anticancer Activity
Current Topics in Medicinal Chemistry FOXM1 and its Oncogenic Signaling in Gastric Cancer
Recent Patents on Anti-Cancer Drug Discovery Pharmacogenetics of Childhood Acute Lymphoblastic Leukemia
Current Pharmacogenomics New Potential Pharmaceutical Applications of Hypericum Species
Mini-Reviews in Medicinal Chemistry Targeting Hypoxia for Sensitization of Tumors to Radio- and Chemotherapy
Current Cancer Drug Targets Neuroglobin and Estrogen Receptors: A New Pathway of Cell Survival and Cell Death Balance
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Role of Oxidative Stress and Anti-Oxidant Treatment in Platinum- Induced Peripheral Neurotoxicity
Current Cancer Drug Targets Peptide Self-Assemblies for Drug Delivery
Current Topics in Medicinal Chemistry