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Research article - Peer-reviewed, 2016

Increased lanosterol turnover: a metabolic burden for daunorubicin-resistant leukemia cells

Staubert, Claudia; Krakowsky, Rosanna; Bhuiyan, Hasanuzzaman; Witek, Barbara; Lindahl, Anna; Broom, Oliver; Nordstrom, Anders


The cholesterol metabolism is essential for cancer cell proliferation. We found the expression of genes involved in the cholesterol biosynthesis pathway up-regulated in the daunorubicin-resistant leukemia cell line CEM/R2, which is a daughter cell line to the leukemia cell line CCRF-CEM (CEM). Cellular (H2O)-H-2 labelling, mass spectrometry, and isotopomer analysis revealed an increase in lanosterol synthesis which was not accompanied by an increase in cholesterol flux or pool size in CEM/R2 cells. Exogenous addition of lanosterol had a negative effect on CEM/R2 and a positive effect on sensitive CEM cell viability. Treatment of CEM and CEM/R2 cells with cholesterol biosynthesis inhibitors acting on the enzymes squalene epoxidase and lanosterol synthase, both also involved in the 24,25-epoxycholesterol shunt pathway, revealed a connection of this pathway to lanosterol turnover. Our data highlight that an increased lanosterol flux poses a metabolic weakness of resistant cells that potentially could be therapeutically exploited.


Leukemia; Drug resistance; Cholesterol biosynthesis; LC-MS; Stable isotope labelling mass spectrometry; Cancer

Published in

Medical Oncology
2016, Volume: 33, article number: 6

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    • Sustainable Development Goals

      SDG3 Good health and well-being

      UKÄ Subject classification

      Cancer and Oncology

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