Abstract
Apoptosis is a defined process for cells to commit suicide through a set of biochemical and morphological cell changes. Activated apoptotic signals converge on the mitochondria, leading to permeabilization of mitochondrial membranes and release of different apoptosis regulatory proteins into the cytosol. With my studies I wanted to investigate the importance of polyamines in the regulation of apoptosis. The homeostasis of polyamines is highly regulated since polyamines are essential for cell proliferation and cell death.
A common feature of polyamine analogue treatment is inhibition of cell proliferation, but sometimes cells also die through apoptosis. When several different breast cancer cell lines were treated with polyamine analogues, mitochondrial activity increased indicating a cellular stress response. The stress response may be caused by polyamine analogue-induced polyamine depletion and/or by the presence of high concentration of a polyamine analogue that does not function as a natural polyamine. Polyamine analogue treatment of L56Br-C1 breast cancer cells resulted in a number of responses culminating in mitochondrial apoptotic cell death, as confirmed by the release of a number of apoptosis-related proteins from the mitochondria.
Another response to analogue treatment was the activation of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT). Using several different methods we have shown that there is an association of SSAT with the mitochondria implicating that SSAT and polyamine depletion are part of the apoptotic process induced by polyamine analogue treatment.
To investigate the role of the antiapoptotic protein Bcl-2 in polyamine analogue-induced apoptosis, a vector carrying the gene for Bcl-2 was introduced into the genome of L56Br-C1 cells. The degree of cell death, polyamine reduction, and SSAT activity decreased in Bcl-2 overexpressing cells compared to control cells.
In conclusion, polyamine analogue treatment clearly affects the mitochondria and can induce apoptosis as a response, something which can be prevented by Bcl-2 overexpression.
A common feature of polyamine analogue treatment is inhibition of cell proliferation, but sometimes cells also die through apoptosis. When several different breast cancer cell lines were treated with polyamine analogues, mitochondrial activity increased indicating a cellular stress response. The stress response may be caused by polyamine analogue-induced polyamine depletion and/or by the presence of high concentration of a polyamine analogue that does not function as a natural polyamine. Polyamine analogue treatment of L56Br-C1 breast cancer cells resulted in a number of responses culminating in mitochondrial apoptotic cell death, as confirmed by the release of a number of apoptosis-related proteins from the mitochondria.
Another response to analogue treatment was the activation of the polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase (SSAT). Using several different methods we have shown that there is an association of SSAT with the mitochondria implicating that SSAT and polyamine depletion are part of the apoptotic process induced by polyamine analogue treatment.
To investigate the role of the antiapoptotic protein Bcl-2 in polyamine analogue-induced apoptosis, a vector carrying the gene for Bcl-2 was introduced into the genome of L56Br-C1 cells. The degree of cell death, polyamine reduction, and SSAT activity decreased in Bcl-2 overexpressing cells compared to control cells.
In conclusion, polyamine analogue treatment clearly affects the mitochondria and can induce apoptosis as a response, something which can be prevented by Bcl-2 overexpression.
| Original language | English |
|---|---|
| Qualification | Doctor |
| Awarding Institution |
|
| Supervisors/Advisors |
|
| Award date | 2006 Oct 13 |
| Publisher | |
| ISBN (Print) | 91-85067-26-1 |
| Publication status | Published - 2006 |
Bibliographical note
Defence detailsDate: 2006-10-13
Time: 09:00
Place: Animal Physiology Building Lecture Hall (1st Floor) Helgonavägen 3B SE-223 62 Lund
External reviewer(s)
Name: Åman, Pierre
Title: Professor
Affiliation: Lundberg Laboratory for Cancer Research, Dept. of Pathology, Göteborg University, Sahlgrenska Univer
---
<div class="article_info">C. Martina Holst and Stina M Oredsson. <span class="article_issue_date">2005</span>. <span class="article_title">Comparison of three cytotoxicity tests in the evaluation of the cytotoxicity of a spermine analogue on human breast cancer cell lines.</span> <span class="journal_series_title">Toxicology In Vitro</span>, <span class="journal_volume">vol 19</span> <span class="journal_pages">pp 379-387</span>. <span class="journal_distributor">Elsevier</span></div>
<div class="article_info">C. Martina Holst, Benjamin Frydman, Laurence J Marton and Stina M Oredsson. <span class="article_issue_date">2006</span>. <span class="article_title">Differential polyamine analogue effects in four different human breast cancer cell lines.</span> <span class="journal_series_title">Toxicology</span>, <span class="journal_volume">vol 223</span> <span class="journal_pages">pp 71-81</span>. <span class="journal_distributor">Elsevier</span></div>
<div class="article_info">C. Martina Holst, Cecilia Hegardt, Johan Staff, Göran Jönsson and Stina M Oredsson. <span class="article_issue_date"></span>. <span class="article_title">Molecular mechanisms in behind N1, N11-diethylnorspermine-induced apoptosis in a human breast cancer cell line.</span> (manuscript)</div>
<div class="article_info">C. Martina Holst, Veronica M Johansson, Kersti Alm and Stina M Oredsson. <span class="article_issue_date"></span>. <span class="article_title">Novel antiapoptotic effects of Bcl-2: Prevention of polyamine depletion-induced cell death.</span> (submitted)</div>
<div class="article_info">C. Martina Holst, Pernilla Nevsten, Fredrik Johansson, Eric Carlemalm and Stina M Oredsson. <span class="article_issue_date"></span>. <span class="article_title">Subcellular distribution of spermidine/spermine N1-acetyltransferase.</span> (manuscript)</div>
The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Department of Cell and Organism Biology (Closed 2011.) (011002100)
Subject classification (UKÄ)
- Biological Sciences
Free keywords
- cancer
- Animal physiology
- Djurfysiologi
- Pharmacological sciences
- pharmacognosy
- pharmacy
- onkologi
- Cytologi
- cancerology
- oncology
- Cytochrome c
- Cytology
- Bcl-2
- Mitochondrial respiration
- Apoptosis
- Human breast cancer cells
- toxicology
- Farmakologi
- farmakognosi
- farmaci
- toxikologi
- Social medicine
- Socialmedicin
- samhällsmedicin
- Mitochondria
- Polyamine analogues
