Abstract
The roles of autophagic cell death and apoptosis induced by topoisomerase inhibitor irinotecan in colon cancer cells with deleted p53 were investigated during 48 h. We report that irinotecan-dependent cytotoxicity and proapoptotic activity were reduced in the present model while autophagy levels significantly increased. Upon p53 transfection, cell demise rates increased, with cells bearing the features of apoptosis and autophagic cell death. The subsequent studies into mechanisms of cell death process revealed the important role of Bax in mediating mitochondrial and lysosomal leakage which might serve as leading signals for both apoptosis and autophagic cell death. These results suggest that different modes of cell death in p53 null colon cancer cells treated with cytostatics (irinotecan) may be activated simultaneously. Moreover, their interactions possibly occur at several stages and aren´t mutually exclusive. This might thus lead to a potential synergism with interesting therapeutic ramifications.
Keywords: Irinotecan, Colon cancer, Autophagy, p53, Chemotherapy, Autophagic cell death, Apoptosis, Bax, Lysosomes, Mitochondria.
Anti-Cancer Agents in Medicinal Chemistry
Title:The Role of Autophagic Cell Death and Apoptosis in Irinotecan-treated p53 Null Colon Cancer Cells
Volume: 13 Issue: 5
Author(s): Stanislav John, Jan Mls, Miroslav Cervinka and Emil Rudolf
Affiliation:
Keywords: Irinotecan, Colon cancer, Autophagy, p53, Chemotherapy, Autophagic cell death, Apoptosis, Bax, Lysosomes, Mitochondria.
Abstract: The roles of autophagic cell death and apoptosis induced by topoisomerase inhibitor irinotecan in colon cancer cells with deleted p53 were investigated during 48 h. We report that irinotecan-dependent cytotoxicity and proapoptotic activity were reduced in the present model while autophagy levels significantly increased. Upon p53 transfection, cell demise rates increased, with cells bearing the features of apoptosis and autophagic cell death. The subsequent studies into mechanisms of cell death process revealed the important role of Bax in mediating mitochondrial and lysosomal leakage which might serve as leading signals for both apoptosis and autophagic cell death. These results suggest that different modes of cell death in p53 null colon cancer cells treated with cytostatics (irinotecan) may be activated simultaneously. Moreover, their interactions possibly occur at several stages and aren´t mutually exclusive. This might thus lead to a potential synergism with interesting therapeutic ramifications.
Export Options
About this article
Cite this article as:
John Stanislav, Mls Jan, Cervinka Miroslav and Rudolf Emil, The Role of Autophagic Cell Death and Apoptosis in Irinotecan-treated p53 Null Colon Cancer Cells, Anti-Cancer Agents in Medicinal Chemistry 2013; 13 (5) . https://dx.doi.org/10.2174/1871520611313050015
DOI https://dx.doi.org/10.2174/1871520611313050015 |
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
-
Guaraná a Caffeine-Rich Food Increases Oxaliplatin Sensitivity of Colorectal HT-29 Cells by Apoptosis Pathway Modulation
Anti-Cancer Agents in Medicinal Chemistry HER3 and its Ligand, Heregulin, as Targets for Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic
Current Gene Therapy Cancer Stem Cells and the Tumor Microenvironment: Soloists or Choral Singers
Current Pharmaceutical Biotechnology Transactivation of EGFR by G Protein-Coupled Receptor in the Pathophysiology of Intimal Hyperplasia
Current Vascular Pharmacology Effects of Salinomycin on Cancer Stem Cell in Human Lung Adenocarcinoma A549 Cells
Medicinal Chemistry Novel Agents in Anticancer Drug Therapy I (Antiangiogenic Agents, Egfr Inhibitors)
Medicinal Chemistry Reviews - Online (Discontinued) Polymorphisms in miRNAs Gene (146a, 149, 196a) and Susceptibility to ARV-associated Hepatotoxicity
Current Genomics Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Current Medicinal Chemistry Tyrosine Kinase Inhibitors
Current Cancer Drug Targets Preparation, Characterization and <i>In Vitro</i> Biological Evaluation of Novel Curcumin Derivatives as Cytotoxic and Apoptosis-Inducing Agents
Anti-Cancer Agents in Medicinal Chemistry Enzyme / Abzyme Prodrug Activation Systems: Potential Use in Clinical Oncology
Current Pharmaceutical Design The Impact of the Activated Stroma on Pancreatic Ductal Adenocarcinoma Biology and Therapy Resistance
Current Molecular Medicine How to Advise Aspirin Use in Patients Who Need NSAIDs
Current Pharmaceutical Design Adverse Effects of Statins - Mechanisms and Consequences
Current Drug Safety Epigenetic Drug Therapy in the Treatment of Colorectal Cancer
Current Pharmaceutical Design The Synthesis of Nano-Doxorubicin and its Anticancer Effect
Anti-Cancer Agents in Medicinal Chemistry Protein Extracts from Somaclonal Mistletoe (Viscum Album L.) Callus with Increased Tumor Cytotoxic Activity in Vitro
Current Bioactive Compounds An Augmented Passive Immune Therapy to Treat Fulminant Bacterial Infections
Recent Patents on Anti-Infective Drug Discovery Potential Anticancer Properties of Bisphosphonates: Insights From Preclinical Studies
Anti-Cancer Agents in Medicinal Chemistry