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Int. J. Mol. Sci. 2017, 18(9), 1982; doi:10.3390/ijms18091982

Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines

1
Ludwig Boltzmann Cluster Oncology, Hanusch Hospital, Vienna 1140, Austria
2
Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna 1140, Austria
3
Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA
*
Author to whom correspondence should be addressed.
Received: 14 July 2017 / Revised: 4 September 2017 / Accepted: 11 September 2017 / Published: 15 September 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Statins and bisphosphonates are increasingly recognized as anti-cancer drugs, especially because of their cholesterol-lowering properties. However, these drugs act differently on various types of cancers. Thus, the aim of this study was to compare the effects of statins and bisphosphonates on the metabolism (NADP+/NADPH-relation) of highly proliferative tumor cell lines from different origins (PC-3 prostate carcinoma, MDA-MB-231 breast cancer, U-2 OS osteosarcoma) versus cells with a slower proliferation rate like MG-63 osteosarcoma cells. Global gene expression analysis revealed that after 6 days of treatment with pharmacologic doses of the statin simvastatin and of the bisphosphonate ibandronate, simvastatin regulated more than twice as many genes as ibandronate, including many genes associated with cell cycle progression. Upregulation of starvation-markers and a reduction of metabolism and associated NADPH production, an increase in autophagy, and a concomitant downregulation of H3K27 methylation was most significant in the fast-growing cancer cell lines. This study provides possible explanations for clinical observations indicating a higher sensitivity of rapidly proliferating tumors to statins and bisphosphonates. View Full-Text
Keywords: statin; bisphosphonate; cancer cell lines; starvation statin; bisphosphonate; cancer cell lines; starvation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Karlic, H.; Haider, F.; Thaler, R.; Spitzer, S.; Klaushofer, K.; Varga, F. Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines. Int. J. Mol. Sci. 2017, 18, 1982.

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