3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines

Craig H. Kuder, Megan M. Weivoda, Ying Zhang, Junjia Zhu, Jeffrey Neighbors, David F. Wiemer, Raymond Hohl

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3-deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X-receptor (LXR) activation. The effects of 3dSB on ATP-binding cassette transporter 1 levels and other LXR targets are similar to that of 25-hydroxycholesterol, an LXR agonist. Unlike 25-hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.

Original languageEnglish (US)
Pages (from-to)1195-1207
Number of pages13
JournalLipids
Volume50
Issue number12
DOIs
StatePublished - Dec 1 2015

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Cultured Cells
Cholesterol
Cells
Cell Line
Liver
Neoplasms
Glioblastoma
ATP Binding Cassette Transporter 1
Homeostasis
Biosynthetic Pathways
Terpenes
Growth
3-deoxyschweinfurthin B
Biological Products
Chemical activation
Liver X Receptors

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Organic Chemistry
  • Cell Biology

Cite this

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title = "3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines",
abstract = "The schweinfurthins have potent antiproliferative activity in multiple glioblastoma multiforme (GBM) cell lines; however, the mechanism by which growth is impeded is not fully understood. Previously, we demonstrated that the schweinfurthins reduce the level of key isoprenoid intermediates in the cholesterol biosynthetic pathway. Herein, we describe the effects of the schweinfurthins on cholesterol homeostasis. Intracellular cholesterol levels are greatly reduced in cells incubated with 3-deoxyschweinfurthin B (3dSB), an analog of the natural product schweinfurthin B. Decreased cholesterol levels are due to decreased cholesterol synthesis and increased cholesterol efflux; both of these cellular actions can be influenced by liver X-receptor (LXR) activation. The effects of 3dSB on ATP-binding cassette transporter 1 levels and other LXR targets are similar to that of 25-hydroxycholesterol, an LXR agonist. Unlike 25-hydroxycholesterol, 3dSB does not act as a direct agonist for LXR α or β. These data suggest that cholesterol homeostasis plays a significant role in the growth inhibitory activity of the schweinfurthins and may elucidate a mechanism that can be targeted in human cancers such as GBM.",
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3-Deoxyschweinfurthin B Lowers Cholesterol Levels by Decreasing Synthesis and Increasing Export in Cultured Cancer Cell Lines. / Kuder, Craig H.; Weivoda, Megan M.; Zhang, Ying; Zhu, Junjia; Neighbors, Jeffrey; Wiemer, David F.; Hohl, Raymond.

In: Lipids, Vol. 50, No. 12, 01.12.2015, p. 1195-1207.

Research output: Contribution to journalArticle

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AU - Zhu, Junjia

AU - Neighbors, Jeffrey

AU - Wiemer, David F.

AU - Hohl, Raymond

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