Evaluating the Effects of Salinomycin and Analogs on the Invasion and Motility of JIMT-1 Breast Cancer Cells
(2014) MOBN30 20132Degree Projects in Molecular Biology
- Abstract
- Abstract
Breast cancer is a disease which affects a large part of the population and is today affecting approximately 1.7 million women worldwide. During the last decade, it has been confirmed that the metastatic ability of cancer is due to cells that detach from the primary tumor and spread to other sites in the body via directed migration. Another aspect which has gained a lot of attention is the occurrence of cancer stem cells (CSCs), and these cells have been theorized to play a main role in cancer relapses. It has been found that salinomycin (Sal), a potassium ionophore isolated from Streptomyces alba, is a selective inhibitor of CSCs. Chemical modification is a means to improve the activity of compounds and the aim of this work... (More) - Abstract
Breast cancer is a disease which affects a large part of the population and is today affecting approximately 1.7 million women worldwide. During the last decade, it has been confirmed that the metastatic ability of cancer is due to cells that detach from the primary tumor and spread to other sites in the body via directed migration. Another aspect which has gained a lot of attention is the occurrence of cancer stem cells (CSCs), and these cells have been theorized to play a main role in cancer relapses. It has been found that salinomycin (Sal), a potassium ionophore isolated from Streptomyces alba, is a selective inhibitor of CSCs. Chemical modification is a means to improve the activity of compounds and the aim of this work was to compare the activity of Sal with four Sal analogs. The analogs and Sal have been found to inhibit CSCs at a 50 nM concentration. The aim of this study was to investigate if the analogs were more effective at hampering migration of JIMT-1 cells than Sal. The effects were studied in vitro using methods such as the wound healing assay, Boyden chamber migration and invasion assays, immunocytochemistry, Western blot and time-laps phase-holographic imaging. The results show that the analogs inhibit migration better than Sal. Overall, these results may present a novel way of treatment of breast cancer in the future and support further work on investigating the possibility of selective targeting of migration and CSCs with Sal analogs. (Less) - Popular Abstract
- Keeping cancer in check
As you modify your computer with the latest software on the market you want it to run faster and work more effectively. When modifying chemicals, you want them to work better and maybe have an effect which suits your field of research. Salinomycin is a chemical which has been modified to be more effective in stopping cancer cells from running amok on the highways in the body. This project seeks to compare the effects of salinomycin to analogs in how they can specifically affect spreading and metastasis formation of breast cancer cells.
The studies conducted in the laboratory were performed on breast cancer cells which were treated with low concentrations of salinomycin or analogs. The first test was to... (More) - Keeping cancer in check
As you modify your computer with the latest software on the market you want it to run faster and work more effectively. When modifying chemicals, you want them to work better and maybe have an effect which suits your field of research. Salinomycin is a chemical which has been modified to be more effective in stopping cancer cells from running amok on the highways in the body. This project seeks to compare the effects of salinomycin to analogs in how they can specifically affect spreading and metastasis formation of breast cancer cells.
The studies conducted in the laboratory were performed on breast cancer cells which were treated with low concentrations of salinomycin or analogs. The first test was to investigate if the migration of cancer cells could be inhibited. This was done by performing a test which mimics wound healing in the body. When cells move in the body, they are looking for nutrients and growth factors. The second test was performed to investigate the migration and chemotactic ability of cancer cells by letting them migrate through a membrane against a nutrient gradient. In the third test, the cancer cells were studied when invading through a gelatinous fluid, or matrigel, which in ways mimics conditions in the body.
When cells are moving around and looking for nutrients, they need a helping hand to anchor them in the correct direction. It was interesting to investigate if these anchors, or proteins, could be affected by treatment. Therefore, protein expressions were analyzed in the cell populations after treatment. These proteins were also analyzed in a microscope being marked with molecules, which emit light with different colors. The last test was to investigate how breast cancer cells move around by studying them in a movie taken with a special microscope based on holographic imaging.
Checkmate cancer?
Chemical modification of a compound is a means to increase its effects, and making better and more effective anti-cancer compounds. The analogs affect the migration of breast cancer cells more effectively than salinomycin when looking at the wound healing and chemotactic ability. However, the results do not explain the mechanism behind these effects. These results may present a novel way of treatment of breast cancer in the future and support further work on investigating the possibility of selective targeting the migration of breast cancer cells.
Advisor: Stina Oredsson
Master´s Degree Project, 45 credits in Toxicology, 2014
Department of Biology, Lund University (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/4530798
- author
- Kempengren, Sebastian
- supervisor
- organization
- course
- MOBN30 20132
- year
- 2014
- type
- H2 - Master's Degree (Two Years)
- subject
- language
- English
- id
- 4530798
- date added to LUP
- 2014-07-04 15:10:33
- date last changed
- 2014-07-04 15:10:33
@misc{4530798,
abstract = {{Abstract
Breast cancer is a disease which affects a large part of the population and is today affecting approximately 1.7 million women worldwide. During the last decade, it has been confirmed that the metastatic ability of cancer is due to cells that detach from the primary tumor and spread to other sites in the body via directed migration. Another aspect which has gained a lot of attention is the occurrence of cancer stem cells (CSCs), and these cells have been theorized to play a main role in cancer relapses. It has been found that salinomycin (Sal), a potassium ionophore isolated from Streptomyces alba, is a selective inhibitor of CSCs. Chemical modification is a means to improve the activity of compounds and the aim of this work was to compare the activity of Sal with four Sal analogs. The analogs and Sal have been found to inhibit CSCs at a 50 nM concentration. The aim of this study was to investigate if the analogs were more effective at hampering migration of JIMT-1 cells than Sal. The effects were studied in vitro using methods such as the wound healing assay, Boyden chamber migration and invasion assays, immunocytochemistry, Western blot and time-laps phase-holographic imaging. The results show that the analogs inhibit migration better than Sal. Overall, these results may present a novel way of treatment of breast cancer in the future and support further work on investigating the possibility of selective targeting of migration and CSCs with Sal analogs.}},
author = {{Kempengren, Sebastian}},
language = {{eng}},
note = {{Student Paper}},
title = {{Evaluating the Effects of Salinomycin and Analogs on the Invasion and Motility of JIMT-1 Breast Cancer Cells}},
year = {{2014}},
}