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05:29
Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
Published on: March 24, 2023
Targeting cell death in tumors by activating caspases
Sarah H MacKenzie1, A Clay Clark
1Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695, USA.
Current Cancer Drug Targets
|March 14, 2008
Summary
Cancer therapies utilize cytotoxic approaches to induce apoptosis, or programmed cell death, in tumor cells. Understanding apoptotic pathways is crucial for developing novel cancer treatments targeting tumor cell eradication.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cytotoxic cancer therapies, including chemotherapy and radiation, induce tumor cell death via apoptosis.
- Apoptosis can be triggered through intrinsic or extrinsic pathways, both involving caspase activation.
- Tumor resistance to therapy may arise from defects in apoptotic signaling pathways.
Purpose of the Study:
- To explore the role of apoptosis in cancer therapy.
- To investigate the interplay between intrinsic and extrinsic apoptotic pathways in tumor cells.
- To identify novel therapeutic strategies for cancer treatment based on apoptotic mechanisms.
Main Methods:
- Review of cell biological, structural, biochemical, and biophysical research on apoptotic pathways.
- Analysis of molecular mechanisms underlying tumor cell sensitivity and resistance to cytotoxic stimuli.
- Exploration of potential therapeutic targets within the apoptotic cascade.
Main Results:
- Cytotoxic agents activate the intrinsic apoptotic pathway, leading to caspase activation and tumor cell death.
- The extrinsic apoptotic pathway enhances tumor cell sensitivity to cytotoxic treatments.
- Defects in apoptotic signaling contribute to tumor resistance to cancer therapies.
Conclusions:
- Apoptotic molecules are critical targets in cancer therapy development.
- Leveraging knowledge of apoptotic pathways can lead to novel compounds for tumor cell eradication.
- Direct activation of executioner caspases, like procaspase-3, presents a promising therapeutic strategy for various cancers.
Related Concept Videos
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:30Apoptosis
Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
01:30Overview of Cell Death
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...