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Induction of apoptosis by cancer chemotherapy
1Division of Oncology Research, Mayo Graduate School, Rochester, Minnesota 55905, USA. Kaufmann.Scott@Mayo.edu
Abstract:
Studies performed over the past five years have demonstrated that there are two major cell-intrinsic pathways for inducing apoptosis, one that begins with ligation of cell surface death receptors and another that involves mitochondrial release of cytochrome c. Several reports have suggested that anticancer drugs kill susceptible cells by inducing expression of death receptor ligands, especially Fas ligand (FasL). Other reports have indicated that chemotherapeutic agents trigger apoptosis by inducing release of cytochrome c from mitochondria. In this review, we describe the two prototypic death pathways, indicate experimental approaches for distinguishing whether chemotherapeutic agents trigger one pathway or the other, summarize current understanding of the role of the two pathways in chemotherapy-induced apoptosis, and discuss the implications of these studies for mechanisms of resistance to chemotherapeutic agents.
Insights
Anticancer drugs induce cell death via two main pathways: death receptor signaling or mitochondrial cytochrome c release. Understanding these apoptosis pathways is crucial for improving chemotherapy effectiveness and overcoming drug resistance.
Area of Science:
- Cellular biology
- Molecular biology
- Pharmacology
Background:
- Apoptosis, or programmed cell death, is a critical process in multicellular organisms.
- Two primary intrinsic cell-death pathways have been identified: the death receptor pathway and the mitochondrial pathway.
- Anticancer drug efficacy is linked to their ability to induce apoptosis in cancer cells.
Purpose of the Study:
- To review the two main pathways of apoptosis.
- To discuss experimental methods for differentiating these pathways in response to chemotherapy.
- To summarize the role of these pathways in chemotherapy-induced apoptosis and drug resistance.
Main Methods:
- Literature review of studies on apoptosis pathways and chemotherapy.
- Analysis of experimental approaches for pathway determination.
- Synthesis of current understanding of chemotherapy-induced apoptosis.
Main Results:
- Chemotherapeutic agents can trigger apoptosis through either the death receptor pathway (e.g., via Fas ligand) or the mitochondrial pathway (cytochrome c release).
- Experimental methods exist to distinguish which pathway is activated by specific drugs.
- The interplay between these pathways influences cancer cell survival and drug response.
Conclusions:
- Distinguishing between the two major apoptosis pathways is essential for understanding chemotherapy mechanisms.
- Knowledge of these pathways can inform strategies to enhance anticancer drug efficacy.
- Understanding these pathways is key to addressing mechanisms of resistance to chemotherapeutic agents.