The role of 15-LOX-1 in resistance to chemotherapeutics

Download
2020
Kazan, Hasan Hüseyin
Chemotherapy is one of the best options to treat cancer. However, drug resistance can limit the efficacy of chemotherapeutics. There have been several reasons for the cancer drug resistance including the export of the drug from cells, inactivation of drugs by enzymatic processes, mutations that limit the binding of the drugs to the target proteins, resistance to cell death mechanism by cellular manipulations and reorganization of the cell membrane. 15-Lipoxygenase-1 (15-LOX-1) is a member of the lipoxygenase family containing iron and catalysing oxygenation of the polyunsaturated fatty acids. Due to this role, 15-LOX-1 is involved in the regulation of critical physiological conditions. However, disruption of the 15-LOX-1-mediated pathway could also trigger pathophysiological conditions, including cancer. There have been numerous reports that combine 15-LOX-1 function and cancer, and 15-LOX-1 is generally regarded as a tumour suppressor protein because of its main product that can activate the apoptosis. Although 15-LOX-1 and cancer relationship has been well defined, the role of 15-LOX-1 in cancer drug resistance has not yet been documented. The present study aims to identify the possible involvement of the 15-LOX-1 protein and its pathways in the cancer drug resistance by focusing particularly on doxorubicin resistance. The results underlined that 15-LOX-1 was downregulated in doxorubicin-resistant cancer cells but the downregulation of 15-LOX-1 was cell and/or drug specific. Moreover, overexpression of 15-LOX-1 in doxorubicin-resistant cancer cells triggered cell death mechanisms in a cell-specific manner and partially re-sensitized the cells towards doxorubicin. Molecular studies revealed that this effect was also cell specific and was a result of cell membrane reorganization in doxorubicin-resistant MCF7 cell line. Still, further molecular and clinical studies are needed to completely explore the role of 15-LOX-1 in cancer drug resistance  

Suggestions

Reversal of breast cancer resistance protein mediated multidrug resistance in MCF7 breast adenocarcinoma cell line
Urfalı, Çağrı; Gündüz, Ufuk; Department of Biology (2011)
Resistance to various chemotherapeutic agents is a major problem in success of cancer chemotherapy. One of the primary reasons of development of multidrug resistance (MDR) is the overexpression of ATP binding cassette (ABC) transporter proteins. Breast cancer resistance protein (BCRP) belongs to ABC transporter family and encoded by ABCG2 gene. BCRP is mainly expressed in MDR1 (P-glycoprotein) lacking breast cancer cells. Overexpression of BCRP leads to efflux of chemotherapeutic agents at higher rates, the...
Synthesis of poly (dl-lactic-co-glycolic acid) coated magnetic nanoparticles for anti-cancer drug delivery
Tansık, Gülistan; Gündüz, Ufuk; Department of Biology (2012)
One of the main problems of current cancer chemotherapy is the lack of selectivity of anti-cancer drugs to tumor cells which leads to systemic toxicity and adverse side effects. In order to overcome these limitations, researches on controlled drug delivery systems have gained much attention. Nanoscale based drug delivery systems provide tumor targeting. Among many types of nanocarriers, superparamagnetic nanoparticles with their biocompatible polymer coatings can be targeted to an intented site by an extern...
Metastatic behaviour of doxorubicin resistant MCF-7 breast cancer cells after Vimentin silencing
Tezcan, Okan; Gündüz, Ufuk; Department of Biology (2013)
Chemotherapy is one of the common treatments in cancer therapy. The effectiveness of chemotherapy is limited by several factors one of which is the emergence of multidrug resistance (MDR). MDR is caused by the activity of diverse ATP binding cassette (ABC) transporters that pump drugs out of the cells. There are several drugs which have been used in treatment of cancer. One of them is doxorubicin that intercalates and inhibits DNA replication. However, doxorubicin has been found to cause development of MDR ...
The Roles of protein kinase d2 in chemoresistant breast cancer cell lines
Alpsoy, Aktan; Gündüz, Ufuk; Department of Biology (2014)
Even though chemotherapy keeps its position as the most preferred and potent strategy of cancer treatment, resistance of tumor to the anti-neoplastic drug poses an obstacle for chemotherapy success. Multidrug resistance (MDR) is a phenomenon that is defined as the intrinsic or acquired resistance against structurally and functionally unrelated drugs. Acquisition of multidrug resistance can be through several distinct mechanisms such as increased drug efflux by ABC transporters, increased drug detoxification...
Investigaton of chemopreventive properties of Urtica Dioica L., in MCF-7 and MDA231 breast cancer cell lines
Güler, Elif; İşcan, Mesude; Department of Biology (2011)
Cancer is a major health problem in developing world with mostly unsufficient treatment. Cancer prevention through dietary modification appears to be a practical and cost effective possibility. The aim of present study is to investigate the chemical components of “Urtica diocia,L (U. diocia) grown in Turkey” and the possible protective potential of its aqueous extract against breast cancer cell lines. U. diocia was extracted by maceration method which was performed for 6,12, 24, and 36 hours, at 50°C, 37°C,...
Citation Formats
H. H. Kazan, “The role of 15-LOX-1 in resistance to chemotherapeutics,” Thesis (Ph.D.) -- Graduate School of Natural and Applied Sciences. Biology., Middle East Technical University, 2020.