Abstract
Indole-3-carbinol (I3C) and its oligomeric derivatives have been widely studied for their chemopreventive and chemotherapeutic properties. We have previously shown that the I3C cyclic tetrameric derivative CTet inhibits breast cancer cell proliferation in vitro and in xenotrasplanted tumor. Here we report the antitumoral activity of a mixture of tri- and tetrameric cyclic I3C derivatives (CTr/CTet) both in vitro (MCF-7 and MDA-MB-231 breast cancer cell lines) and in vivo in a tumor xenograft model. CTr/CTet mixture avoids the low solubility drawbacks of CTet, thus favouring its solubilization, and reducing purification process, time and costs. CTr/CTet mixture has been shown to inhibit breast cancer cell proliferation (IC50 = 1.3 and 1.6 μg/ml in MCF-7 and MDAMB- 231, respectively) inducing the G0/1 cell cycle phase accumulation. The main molecular events related to CTr/CTet activity are the overexpression of p21, p27 and GADD45A, nuclear translocation of FOXO3a, inhibition of Akt activity and downregulation of estrogen receptor. In vivo, the growth of xenotransplanted tumor has been inhibited and the pro-tumoral low molecular weight cyclin E downregulation has been detected. Our data indicate that CTr/CTet is a potential anticancer combination agent for both hormoneresponsive and triple-negative breast tumors.
Keywords: Akt, Breast Cancer, FOXO3a, GADD45A, I3C cyclic derivatives, LMW cyclin E, CTr/CTet, p21/CDKN1A, p27/CDKN1B
Anti-Cancer Agents in Medicinal Chemistry
Title:Antitumoral Activity of Indole-3-carbinol Cyclic tri- and Tetrameric Derivatives Mixture in Human Breast Cancer Cells: In Vitro and In Vivo Studies
Volume: 13 Issue: 4
Author(s): Giorgio Brandi, Alessandra Fraternale, Simone Lucarini, Mirko Paiardini, Mauro De Santi, Barbara Cervasi, Maria F. Paoletti, Luca Galluzzi, Andrea Duranti and Mauro Magnani
Affiliation:
Keywords: Akt, Breast Cancer, FOXO3a, GADD45A, I3C cyclic derivatives, LMW cyclin E, CTr/CTet, p21/CDKN1A, p27/CDKN1B
Abstract: Indole-3-carbinol (I3C) and its oligomeric derivatives have been widely studied for their chemopreventive and chemotherapeutic properties. We have previously shown that the I3C cyclic tetrameric derivative CTet inhibits breast cancer cell proliferation in vitro and in xenotrasplanted tumor. Here we report the antitumoral activity of a mixture of tri- and tetrameric cyclic I3C derivatives (CTr/CTet) both in vitro (MCF-7 and MDA-MB-231 breast cancer cell lines) and in vivo in a tumor xenograft model. CTr/CTet mixture avoids the low solubility drawbacks of CTet, thus favouring its solubilization, and reducing purification process, time and costs. CTr/CTet mixture has been shown to inhibit breast cancer cell proliferation (IC50 = 1.3 and 1.6 μg/ml in MCF-7 and MDAMB- 231, respectively) inducing the G0/1 cell cycle phase accumulation. The main molecular events related to CTr/CTet activity are the overexpression of p21, p27 and GADD45A, nuclear translocation of FOXO3a, inhibition of Akt activity and downregulation of estrogen receptor. In vivo, the growth of xenotransplanted tumor has been inhibited and the pro-tumoral low molecular weight cyclin E downregulation has been detected. Our data indicate that CTr/CTet is a potential anticancer combination agent for both hormoneresponsive and triple-negative breast tumors.
Export Options
About this article
Cite this article as:
Brandi Giorgio, Fraternale Alessandra, Lucarini Simone, Paiardini Mirko, De Santi Mauro, Cervasi Barbara, F. Paoletti Maria, Galluzzi Luca, Duranti Andrea and Magnani Mauro, Antitumoral Activity of Indole-3-carbinol Cyclic tri- and Tetrameric Derivatives Mixture in Human Breast Cancer Cells: In Vitro and In Vivo Studies, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (4) . https://dx.doi.org/10.2174/1871520611313040014
DOI https://dx.doi.org/10.2174/1871520611313040014 |
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
-
Synthesis and Cytotoxic Activity of Steroidal Phosphorothioate,Phosphoroselenoate, and Phosphate Derivatives Conjugated with 3-Azido-3-Deoxythymidine
Letters in Organic Chemistry Cucurbitacin E, An Experimental Lead Triterpenoid with Anticancer, Immunomodulatory and Novel Effects Against Degenerative Diseases. A Mini-Review
Current Topics in Medicinal Chemistry Trifluoroibuprofen Inhibits α-Methylacyl Coenzyme A Racemase (AMACR/P504S), Reduces Cancer Cell Proliferation and Inhibits in vivo Tumor Growth in Aggressive Prostate Cancer Models
Anti-Cancer Agents in Medicinal Chemistry Synthesis and In Vitro Biochemical Evaluation of a Series of Compounds as Potential Inhibitors of Estrone Sulfatase (ES) and the Role of pKa in both the Synthesis and the Inhibitory Activity of the Potential Inhibitors
Letters in Drug Design & Discovery Proline Oxidase (POX) as A Target for Cancer Therapy
Current Drug Targets New Multidrug Resistance Reversal Agents
Current Drug Targets Targeted Alpha Therapy with 227Th-trastuzumab of Intraperitoneal Ovarian Cancer in Nude Mice
Current Radiopharmaceuticals Bioconjugation of Ionophore Antibiotics: A Way to Obtain Hybrids with Potent Biological Activity
Mini-Reviews in Organic Chemistry The Role of Epithelial-Mesenchymal Interactions in Tissue Repair, Fibrogenesis and Carcinogenesis
Current Signal Transduction Therapy Extracellular HSP90: An Emerging Target for Cancer Therapy
Current Signal Transduction Therapy Integrin-Targeted Peptide- and Peptidomimetic-Drug Conjugates for the Treatment of Tumors
Recent Patents on Anti-Cancer Drug Discovery Vitamin D and the Adaptive Immune System with Special Emphasis to Allergic Reactions and Allograft Rejection
Inflammation & Allergy - Drug Targets (Discontinued) Curcumin Exposure Modulates Multiple Pro-Apoptotic and Anti-Apoptotic Signaling Pathways to Antagonize Acetaminophen-Induced Toxicity
Current Neurovascular Research The Crosstalk between Tissue Engineering and Pharmaceutical Biotechnology: Recent Advances and Future Directions
Current Pharmaceutical Biotechnology Microarray: An Approach for Current Drug Targets
Current Drug Metabolism Tissue Distribution and Pharmacodynamics: A Complicated Relationship
Current Drug Metabolism Solanum nigrum Anticancer Effect Through Epigenetic Modulations in Breast Cancer Cell Lines
Current Cancer Therapy Reviews ADAM9 as a Potential Target Molecule in Cancer
Current Pharmaceutical Design HIF Prolyl 4-Hydroxylases and their Potential as Drug Targets
Current Pharmaceutical Design The Diagnostic Utility of Pleural Fluid Tests in Clinical Practice
Current Respiratory Medicine Reviews