Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells
A A Danen-Van Oorschot1, D F Fischer, J M Grimbergen
1Laboratory for Molecular Carcinogenesis, Sylvius Laboratory, Leiden University, P.O. Box 9503, 2300 RA Leiden, The Netherlands.
Abstract:
The chicken anemia virus protein apoptin induces a p53-independent, Bcl-2-insensitive type of apoptosis in various human tumor cells. Here, we show that, in vitro, apoptin fails to induce programmed cell death in normal lymphoid, dermal, epidermal, endothelial, and smooth-muscle cells. However, when normal cells are transformed they become susceptible to apoptosis by apoptin. Long-term expression of apoptin in normal human fibroblasts revealed that apoptin has no toxic or transforming activity in these cells. In normal cells, apoptin was found predominantly in the cytoplasm, whereas in transformed and malignant cells it was located in the nucleus, suggesting that the localization of apoptin is related to its activity. These properties make apoptin a potential agent for the treatment of a large number of tumors, also those lacking p53 and/or overexpressing Bcl-2.
Insights
Chicken anemia virus protein apoptin selectively induces apoptosis in tumor cells, not normal cells. Its nuclear localization in cancer cells suggests potential as a targeted cancer therapy, even for tumors resistant to conventional treatments.
Area of Science:
- Oncology
- Virology
- Cell Biology
Background:
- Chicken anemia virus (CAV) protein apoptin induces apoptosis in various human tumor cells.
- Apoptin-induced apoptosis is independent of p53 and Bcl-2 pathways.
- Normal cells are generally resistant to apoptin-induced cell death.
Purpose of the Study:
- To investigate the differential effects of apoptin on normal versus transformed/malignant human cells.
- To explore the role of apoptin localization in its apoptotic activity.
- To assess the therapeutic potential of apoptin for cancer treatment.
Main Methods:
- In vitro assays to test apoptin's effect on various normal and transformed human cell types.
- Long-term expression studies in normal human fibroblasts.
- Subcellular localization studies of apoptin in different cell types using microscopy.
Main Results:
- Apoptin selectively induced apoptosis in transformed and malignant cells but not in normal lymphoid, dermal, epidermal, endothelial, or smooth-muscle cells.
- Normal human fibroblasts expressing apoptin long-term showed no toxicity or transforming activity.
- Apoptin localized predominantly in the cytoplasm of normal cells and in the nucleus of transformed/malignant cells.
Conclusions:
- Apoptin's selective induction of apoptosis in tumor cells, coupled with its nuclear localization in these cells, highlights its potential as a targeted cancer therapeutic.
- Apoptin may be effective against a broad range of tumors, including those resistant to p53-dependent or Bcl-2-mediated apoptosis.
More Related Videos
09:18Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
09:57Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
Published on: January 29, 2019
Related Concept Videos
Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Apoptosis
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
