15-LOX-1 has diverse roles in the resensitization of resistant cancer cell lines to doxorubicin

Date

2020-05-01

Author

Kazan, Hasan Huseyin
Urfali-Mamatoglu, Cagri
Yalcin, Gizem Damla
Bulut, Onur
Sezer, Abdullah
Banerjee, Sreeparna
Gündüz, Ufuk

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Lipoxygenases (LOXs) are a family of enzymes that can oxygenate polyunsaturated fatty acids. As a member of the family, 15-lipoxygenase-1 (15-LOX-1) specifically metabolizes arachidonic acid and linoleic acid. 15-LOX-1 can affect physiological and pathophysiological events via regulation of the protein-lipid interactome, alterations in intracellular redox state and production of lipid metabolites that are involved in the induction and resolution of inflammation. Although several studies have shown that 15-LOX-1 has an antitumorigenic role in many different cancer models, including breast cancer, the role of the protein in cancer drug resistance has not been established yet. In this study, we, for the first time, aimed to show the potential role of 15-LOX-1 in acquired doxorubicin (DOX) resistance in MCF7 and HeLa cancer cell lines. Our results show that ALOX15 was transcriptionally downregulated in DOX-resistant cells compared with their drug-sensitive counterparts. Moreover, overexpression of ALOX15 in the drug-resistant cells resulted in resensitization of those cells to DOX in a cell-dependent manner. 15-LOX-1 expression could induce apoptosis by activating PPAR gamma and enhance the accumulation of DOX in drug-resistant MCF7 cells by altering cellular motility properties, and membrane dynamics. However, HeLa DOX cells did not show any of these effects but were susceptible to cell death when treated with 13(S)-HODE. These results underline the role and importance of 15-LOX-1 in cancer drug resistance, and points to novel mechanisms as a therapeutic approach to overcome cancer drug resistance.

Subject Keywords

15-LOX-1, Cancer drug resistance, Cell motility, Doxorubicin, PPAR gamma

URI

https://hdl.handle.net/11511/30108

Journal

JOURNAL OF CELLULAR PHYSIOLOGY

DOI

https://doi.org/10.1002/jcp.29375

Collections

Graduate School of Natural and Applied Sciences, Article

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Citation Formats

H. H. Kazan et al., “15-LOX-1 has diverse roles in the resensitization of resistant cancer cell lines to doxorubicin,” JOURNAL OF CELLULAR PHYSIOLOGY, pp. 4965–4978, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/30108.