Abstract
The evasion of cancer cells from the induction of cell death pathways results in the resistance of tumor to current treatment modalities. Therefore, the resistance to cell death, one of the hallmarks of cancer, is a major target in the development of new approaches to selectively affect cancer cells. The complex interplay between individual members of Bcl-2 family regulates both cell survival and the mitochondrial pathway of apoptosis by maintaining mitochondrial membrane integrity (anti-apoptotic Bcl-2 subfamily) and by triggering its disruption in response to stress stimuli (Bax-like subfamily). BH3-only proteins, another Bcl-2 subfamily, act either by direct stimulation of pro-apoptotic proteins of the Bax subfamily or by interfering with anti-apoptotic proteins of the Bcl-2 subfamily. Thus, pro-apoptotic BH3 mimetics, thought to function as BH3-only proteins, are expected to improve the effectiveness of cancer treatment. BH3 mimetics could be either natural or synthetic, peptidic or only based on a helical peptide-like scaffold. Experimental and clinical evidence indicates that BH3 mimetics may not be sufficient to cure cancer patients when used as a single agent. BH3 profiling of cancer cells was introduced to better predict the in vivo responsiveness of tumor to BH3 mimetics combined with conventional therapies. In summary, targeting the Bcl-2 proteins is a promising tool with potential to generate new treatment modalities and to complement existing anti-cancer therapies. This review presents the current knowledge on BH3-only proteins and the spectrum of strategies employing BH3 mimetics in preclinical and clinical studies that aim at tumor targeting.
Keywords: ABT-737, Antimycin A, Apoptosis, Anti-cancer therapy, Autophagy, Bcl-2 proteins, BH3 domain, BH3 mimetics, BH3-only proteins, BH3 peptide, Gossypol, HA14-1, Obatoclax, SAHB, S1, TW-37
Anti-Cancer Agents in Medicinal Chemistry
Title:Pro-apoptotic Activity of BH3-only Proteins and BH3 Mimetics: from Theory to Potential Cancer Therapy
Volume: 12 Issue: 8
Author(s): Mariusz L. Hartman and Malgorzata Czyz
Affiliation:
Keywords: ABT-737, Antimycin A, Apoptosis, Anti-cancer therapy, Autophagy, Bcl-2 proteins, BH3 domain, BH3 mimetics, BH3-only proteins, BH3 peptide, Gossypol, HA14-1, Obatoclax, SAHB, S1, TW-37
Abstract: The evasion of cancer cells from the induction of cell death pathways results in the resistance of tumor to current treatment modalities. Therefore, the resistance to cell death, one of the hallmarks of cancer, is a major target in the development of new approaches to selectively affect cancer cells. The complex interplay between individual members of Bcl-2 family regulates both cell survival and the mitochondrial pathway of apoptosis by maintaining mitochondrial membrane integrity (anti-apoptotic Bcl-2 subfamily) and by triggering its disruption in response to stress stimuli (Bax-like subfamily). BH3-only proteins, another Bcl-2 subfamily, act either by direct stimulation of pro-apoptotic proteins of the Bax subfamily or by interfering with anti-apoptotic proteins of the Bcl-2 subfamily. Thus, pro-apoptotic BH3 mimetics, thought to function as BH3-only proteins, are expected to improve the effectiveness of cancer treatment. BH3 mimetics could be either natural or synthetic, peptidic or only based on a helical peptide-like scaffold. Experimental and clinical evidence indicates that BH3 mimetics may not be sufficient to cure cancer patients when used as a single agent. BH3 profiling of cancer cells was introduced to better predict the in vivo responsiveness of tumor to BH3 mimetics combined with conventional therapies. In summary, targeting the Bcl-2 proteins is a promising tool with potential to generate new treatment modalities and to complement existing anti-cancer therapies. This review presents the current knowledge on BH3-only proteins and the spectrum of strategies employing BH3 mimetics in preclinical and clinical studies that aim at tumor targeting.
Export Options
About this article
Cite this article as:
L. Hartman Mariusz and Czyz Malgorzata, Pro-apoptotic Activity of BH3-only Proteins and BH3 Mimetics: from Theory to Potential Cancer Therapy, Anti-Cancer Agents in Medicinal Chemistry 2012; 12 (8) . https://dx.doi.org/10.2174/187152012802650084
DOI https://dx.doi.org/10.2174/187152012802650084 |
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
-
Review on EGFR Inhibitors: Critical Updates
Mini-Reviews in Medicinal Chemistry Based on Nucleotides Analysis of Tumor Cell Lines to Construct and Validate a Prediction Model of Mechanisms of Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Assortment of Human Amniotic Membrane and Curcumin: a Potential Therapeutic Strategy for Burn Wound Healing
Current Drug Therapy Molecular Link Mechanisms between Inflammation and Cancer
Current Pharmaceutical Design Sorafenib (BAY 43-9006) in Hepatocellular Carcinoma Patients: From Discovery to Clinical Development
Current Medicinal Chemistry Evaluating Gene Delivery Using N-triethyl Chitosan Nanoparticles to AsPC-1 Cells and Predicting the Relation between Transfection, Cytotoxicity and Charge Ratio of Nanoparticles Via Mathematical Models
Drug Delivery Letters New Perspectives in the Pharmacological Potential of Naringin in Medicine
Current Medicinal Chemistry Process Variables and Design of Experiments in Liposome and Nanoliposome Research
Mini-Reviews in Medicinal Chemistry Telomerase Inhibitors: Potential Anticancer Agents
Mini-Reviews in Organic Chemistry Potential Role of Rho Kinase Inhibitors in Combating Diabetes-Related Complications Including Diabetic Neuropathy-A Review
Current Diabetes Reviews Stem Cell Function, Self-Renewal, Heterogeneity, and Regenerative Potential in Skeletal Muscle Stem Cells
Recent Patents on Regenerative Medicine MicroRNAs in Tumorigenesis
Current Pharmaceutical Biotechnology Pleiotropic Effects of Cardioactive Glycosides
Current Medicinal Chemistry Electronic Noses in Medical Diagnostics
Current Medicinal Chemistry Membrane Interacting Peptides: A Review
Current Protein & Peptide Science Poly (ADP-Ribosyl) Polymerase 1 Inhibitors: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery Generation of Human Single-chain Antibody to the CD99 Cell Surface Determinant Specifically Recognizing Ewing’s Sarcoma Tumor Cells
Current Pharmaceutical Biotechnology Drug-Targeting Strategies for Prostate Cancer
Current Pharmaceutical Design Curcumin Conjugates and Metallocomplexes as Lead Compounds for Development of Anticancer Agents - A Short Review
Current Bioactive Compounds Lanthanum, Gallium and their Impact on Oxidative Stress
Current Medicinal Chemistry