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Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Chemistry. Linköping University, The Institute of Technology.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
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2014 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 7, 628-635 p.Article in journal (Refereed) Published
Abstract [en]

Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014. Vol. 85A, no 7, 628-635 p.
Keyword [en]
cancer stem cells; luminescent conjugated oligothiophenes; fluorescent probes
National Category
Clinical Medicine Chemical Sciences Medical Biotechnology Computer and Information Science
Identifiers
URN: urn:nbn:se:liu:diva-109171DOI: 10.1002/cyto.a.22437ISI: 000338007700010PubMedID: 24500794OAI: oai:DiVA.org:liu-109171DiVA: diva2:737380
Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Poly-and oligothiophenes: Optical probes for multimodal fluorescent assessment of biological processes
Open this publication in new window or tab >>Poly-and oligothiophenes: Optical probes for multimodal fluorescent assessment of biological processes
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

One interesting class of molecules in the research field of imaging biological processes is luminescent conjugated polythiophenes, LCPs. These fluorescent probes have a flexible backbone consisting of repetitive thiophene units. Due to this backbone, the probes possess unique abilities to give rise to different spectral signatures depending on their target and environment. LCPs are a polydispersed material meaning there is an uneven distribution of lengths of the probe. Recently, monodispersed chemically well-defined material denoted luminescent conjugated oligothiophenes, LCOs, with an exact number of repetitive units and distinct sidechain functionalities along the backbone has been developed. LCOs have the advantages of being smaller which leads to higher ability to cross the blood brain barrier. The synthesis of minor chemical alterations is also more simplified due to the well-defined materials.

During my doctoral studies I have used both LCPs and LCOs to study biological processes such as conformational variation of protein aggregates in prion diseases and cellular uptake in normal cells and cancer cells. The research has generally been based on the probes capability to emit light upon irradiation and the interaction with their targets has mainly been assessed through variations in fluorescence intensity, emission-and excitation profiles and fluorescence lifetime decay. These studies verified the utility of LCPs and LCOs for staining and discrimination of both prion strains and cell phenotypes. The results also demonstrated the pronounced influence minor chemical modifications have on the LCO´s staining capacity.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. 54 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1693
National Category
Chemical Sciences Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-121815 (URN)10.3384/diss.diva-121815 (DOI)978-91-7685-986-5 (ISBN)
Public defence
2015-11-06, Planck, Fysikhuset, Campus Valla, Linköping, 10:15 (Swedish)
Opponent
Supervisors
Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2015-10-07Bibliographically approved
2. PKB/Akt kinase localization and role in stemness maintenance in cancer
Open this publication in new window or tab >>PKB/Akt kinase localization and role in stemness maintenance in cancer
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cancer incidence rates have increased over the last decade. Currently available therapies are only moderately effective in targeting cancer cells. Established cancer treatment protocols fail to eliminate populations of cancer stem cells (CSCs), which develop resistance against the chemotherapeutic drugs and lead to cancer recurrence. Therefore, understanding the mechanisms by which CSCs resist drugs and identifying molecular markers are both necessary to further improve prognosis and to develop new treatment strategies. Increased protein kinase B/Akt1 gene expression and/or activity have been found increased in majority of cancer types. Akt1 is a key player in PI3K-AktmTOR pathway that is vital for cell survival, proliferation, migration, invasion, metastasis, angiogenesis and apoptosis. In this study, we investigated a series of novel markers to improve the characterization of CSCs, with particular focus the roles of Akt in CSC maintenance and the regulatory role of micro-RNA (miR) in cancer cells. While utilizing in breast cancer cells as models, we found that luminescent conjugated oligothiophenes (LCOs), p-HTMI and p-HTAA have the potential to differentially stain various subpopulations of cancer cells, presumably also CSCs among breast cancer cells. However, further studies are needed to confirm these results. Additionally, when we investigated the effect of Akt intracellular compartmentalization on CSC development, the results revealed that nuclear Akt enhances CSC proliferation (ALDH +/High CD44+/High/CD24-/Low) and clonogenicity, which was counter examined and confirmed by using the Aktspecific inibitor triciribine. Furthermore, while investigating the impact of Akt on miR regulation in cancer cells, we found that Akt overexpression decreased.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 60 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1515
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-127477 (URN)10.3384/diss.diva-127477 (DOI)978-91-7685-806-6 (ISBN)
Public defence
2016-06-01, Belladonna, Campus US, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2016-04-27 Created: 2016-04-27 Last updated: 2016-04-27Bibliographically approved

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