Abstract
The PI3K/Akt signaling pathway mediates mitogen-dependent growth and survival in various types of cancer cells, and inhibition of this pathway results in tumor cell growth arrest and apoptosis. Tocotrienols are natural forms of vitamin E that displays potent anticancer activity at treatment doses that had little or no effect on normal cell viability. Mechanistic studies revealed that the anticancer effects of γ-tocotrienol were associated with a suppression in PI3K/Akt signaling. Additional studies showed that cytotoxic LD50 doses of γ-tocotrienol were 3-5-fold higher than growth inhibitory IC50 treatment doses, suggesting that cytotoxic and antiproliferative effects of γ-tocotrienol might be mediated through different mechanisms. However, γ-tocotrienol-induced caspase activation and apoptosis in mammary tumor cells was also found to be associated with suppression in intracellular PI3K/Akt signaling and subsequent down-regulation of FLIP, an endogenous inhibitor of caspase processing and activation. Since breast cancer cells are significantly more sensitive to the inhibitory effects of γ-tocotrienol on PI3K/Akt signaling than normal cells, these findings suggest that γ-tocotrienol may provide significant health benefits in reducing the risk of breast cancer in women. Studies have also shown that combined treatment of γ-tocotrienol with other chemotherapeutic agents can result in a synergistic anticancer response. Combination therapy was most effective when the anticancer mechanism of action of γ-tocotrienol is complimentary to that of the other drug and can provide significant health benefits in the prevention and/or treatment of breast cancer, while at the same time avoiding tumor resistance or toxic effects that is commonly associated with high dose monotherapy.
Keywords: Vitamin E, tocotrienols, PI3K, Akt, breast cancer.
Anti-Cancer Agents in Medicinal Chemistry
Title:Tocotrienols Target PI3K/Akt Signaling in Anti-Breast Cancer Therapy
Volume: 13 Issue: 7
Author(s): Paul W. Sylvester and Nehad M. Ayoub
Affiliation:
Keywords: Vitamin E, tocotrienols, PI3K, Akt, breast cancer.
Abstract: The PI3K/Akt signaling pathway mediates mitogen-dependent growth and survival in various types of cancer cells, and inhibition of this pathway results in tumor cell growth arrest and apoptosis. Tocotrienols are natural forms of vitamin E that displays potent anticancer activity at treatment doses that had little or no effect on normal cell viability. Mechanistic studies revealed that the anticancer effects of γ-tocotrienol were associated with a suppression in PI3K/Akt signaling. Additional studies showed that cytotoxic LD50 doses of γ-tocotrienol were 3-5-fold higher than growth inhibitory IC50 treatment doses, suggesting that cytotoxic and antiproliferative effects of γ-tocotrienol might be mediated through different mechanisms. However, γ-tocotrienol-induced caspase activation and apoptosis in mammary tumor cells was also found to be associated with suppression in intracellular PI3K/Akt signaling and subsequent down-regulation of FLIP, an endogenous inhibitor of caspase processing and activation. Since breast cancer cells are significantly more sensitive to the inhibitory effects of γ-tocotrienol on PI3K/Akt signaling than normal cells, these findings suggest that γ-tocotrienol may provide significant health benefits in reducing the risk of breast cancer in women. Studies have also shown that combined treatment of γ-tocotrienol with other chemotherapeutic agents can result in a synergistic anticancer response. Combination therapy was most effective when the anticancer mechanism of action of γ-tocotrienol is complimentary to that of the other drug and can provide significant health benefits in the prevention and/or treatment of breast cancer, while at the same time avoiding tumor resistance or toxic effects that is commonly associated with high dose monotherapy.
Export Options
About this article
Cite this article as:
Sylvester W. Paul and Ayoub M. Nehad, Tocotrienols Target PI3K/Akt Signaling in Anti-Breast Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (7) . https://dx.doi.org/10.2174/18715206113139990116
DOI https://dx.doi.org/10.2174/18715206113139990116 |
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
-
Molecular Mechanisms Underlying Psychological Stress and Cancer
Current Pharmaceutical Design Better Predictive Value of Cancer Antigen125 (CA125) as Biomarker in Ovary and Breast Tumors and its Correlation with the Histopathological Type/Grade of the Disease
Medicinal Chemistry Computational Approaches for Translational Oncology: Concepts and Patents
Recent Patents on Anti-Cancer Drug Discovery The Potential Use of Peptides in Cancer Treatment
Current Protein & Peptide Science Polyphenols Beyond Barriers: A Glimpse into the Brain
Current Neuropharmacology BSA Au Clusters as a Probe for Enhanced Fluorescence Detection Using Multipulse Excitation Scheme
Current Pharmaceutical Biotechnology Genotoxicity of Nanocarriers
Current Drug Metabolism Nanoparticle Albumin - Bound (NAB) Technology is a Promising Method for Anti-Cancer Drug Delivery
Recent Patents on Anti-Cancer Drug Discovery Src Family Kinases: Potential Targets for the Treatment of Human Cancer and Leukemia
Current Pharmaceutical Design Nuclear Hormone Receptor Signals as New Therapeutic Targets for Urothelial Carcinoma
Current Cancer Drug Targets Synthetic Curcumin Analog UBS109 Inhibits the Growth of Head and Neck Squamous Cell Carcinoma Xenografts
Current Cancer Drug Targets Box-Behnken Design Optimized TPGS Coated Bovine Serum Albumin Nanoparticles Loaded with Anastrozole
Current Drug Delivery Development and Validation of a Highly Sensitive HPLC Method for Determination of Paclitaxel in Pharmaceutical Dosage forms and Biological Samples
Current Pharmaceutical Analysis ERRATUM
Current Cancer Drug Targets The 21st Century Form of Vitamin E - Tocotrienol
Current Pharmaceutical Design The Potential Use of Hormone-Based Therapeutics for the Treatment of Alzheimers Disease
Current Alzheimer Research Design and Development of Nanoemulsion Systems Containing Interferon Gamma
Protein & Peptide Letters Developmental Expression and Dysregulation of miR-146a and miR-155 in Down's Syndrome and Mouse Models of Down's Syndrome and Alzheimer's Disease
Current Alzheimer Research The Ayurvedic Bhasma: The Ancient Science of Nanomedicine
Recent Patents on Nanomedicine Novel Compounds from Marine Microorganisms that Inhibit Mammalian DNA Polymerase
Current Organic Chemistry