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Induction of apoptosis--new targets for cancer chemotherapy
C Dive1, C A Evans, A D Whetton
1Cancer Research Campaign Cellular and Molecular Pharmacology Group, School of Biological Sciences, Manchester University, UK.
Abstract:
Many anticancer agents induce an active cell death process, apoptosis, in sensitive tumour cells. Elucidation of molecular mechanisms underlying apoptosis may shed light on why some tumour cells survive chemotherapy, and may identify new targets for anticancer agents whose effects are not tightly linked to proliferative status. The signal transduction events which initiate apoptosis are unclear. A change in cytosolic calcium is generally assumed to be a key signal for apoptosis although the evidence for this is not conclusive. Other putative signal transducers which may modulate apoptosis are protein kinase C and cAMP. Genes which induce apoptosis in response to such signals are largely unidentified, but certain oncogenes, notably bcl-2, act to delay or suppress apoptosis in several cell types.
Insights
Understanding cancer cell death is key to improving chemotherapy. This study explores the molecular signals, like calcium and protein kinase C, that trigger apoptosis, and identifies genes such as bcl-2 that can prevent it.
Area of Science:
- Molecular Biology
- Cellular Biology
- Cancer Research
Background:
- Anticancer agents often induce apoptosis, a programmed cell death process, in sensitive tumor cells.
- Understanding the molecular mechanisms of apoptosis is crucial for improving chemotherapy efficacy and identifying new therapeutic targets.
- The precise signal transduction pathways initiating apoptosis remain unclear, with a debated role for cytosolic calcium.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying apoptosis in cancer cells.
- To investigate potential signal transduction events that initiate or modulate apoptosis.
- To identify genes involved in apoptosis regulation, particularly those that may confer resistance to chemotherapy.
Main Methods:
- Review and analysis of existing literature on apoptosis signaling pathways.
- Examination of the roles of key signaling molecules such as cytosolic calcium, protein kinase C, and cAMP.
- Investigation of the function of specific genes, including oncogenes like bcl-2, in the regulation of apoptosis.
Main Results:
- The exact signaling pathways that trigger apoptosis are not fully understood.
- While a change in cytosolic calcium is often assumed to be a key signal, conclusive evidence is lacking.
- Certain oncogenes, notably bcl-2, have been identified as suppressors of apoptosis in various cell types.
Conclusions:
- Further research is needed to clarify the signal transduction events initiating apoptosis.
- Identifying the molecular regulators of apoptosis can lead to novel anticancer strategies.
- Understanding mechanisms of apoptosis resistance, such as bcl-2 activity, is vital for overcoming treatment failure.