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
-
Computational Method for Identifying Malonylation Sites by Using Random Forest Algorithm
Combinatorial Chemistry & High Throughput Screening Editorial (Thematic Issue: Gene Therapy for Gastrointestinal and Liver Cancers: Past Experience, Current Status and Future Perspectives)
Current Gene Therapy Discovery Approaches for Novel Dyslipidemia Drugs
Current Drug Discovery Technologies Subject Index to Volume 10
Current Medicinal Chemistry The Molecular Mechanisms of TRAIL Resistance in Cancer Cells: Help in Designing New Drugs
Current Pharmaceutical Design Angiogenesis Markers in Gynecological Tumors and Patents for Anti- Angiogenic Approach: Review
Recent Patents on Anti-Cancer Drug Discovery Reprograming Carcinoma Associated Fibroblasts by microRNAs
Current Molecular Medicine γ-Secretase Substrates and their Implications for Drug Development in Alzheimer's Disease
Current Topics in Medicinal Chemistry Glycine Transporter Type-1 and its Inhibitors
Current Medicinal Chemistry Head and Neck Cancer Treatments through Chemotherapy to Magnetic Systems: Perspectives and Challenges
Current Radiopharmaceuticals Resveratrol as an Enhancer of Apoptosis in Cancer: A Mechanistic Review
Anti-Cancer Agents in Medicinal Chemistry Chronopharmacology and Antimicrobial Therapeutics
Current Clinical Pharmacology MicroRNA in the Pathogenesis and Prognosis of Esophageal Cancer
Current Pharmaceutical Design The Impacts of Non-coding RNAs and N<sup>6</sup>-Methyladenosine on Cancer: Past, Present and Future
Current Cancer Drug Targets Molecular Pathways, Screening and Follow-up of Colorectal Carcinogenesis: An Overview
Current Cancer Therapy Reviews Integrin αvβ3 Antagonists for Anti-Angiogenic Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Using Cheminformatics for the Identification of Biological Functions of Small Molecules in Metabolic Pathway
Current Topics in Medicinal Chemistry Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment
Current Cancer Drug Targets Analytical Techniques for DNA Methylation – An Overview
Current Pharmaceutical Analysis Monoclonal Antobodies: Application in Radiopharmacy
Current Radiopharmaceuticals