Schweinfurthins: Lipid Modulators with Promising Anticancer Activity
Abstract
The schweinfurthin family of compounds displays exciting potent and differential cytotoxicity against human cancer cell lines. Currently, the effect of schweinfurthins on tumor development and progression is being explored in animal models of cancer with promising results. The first schweinfurthin family member, vedelianin, was isolated in 1992, followed by other schweinfurthins in 1998. This opened up the door for the synthesis of additional analogs. At present, the focus of research lies on delineating the mechanism of schweinfurthin action and identifying the nature of sensitivity. It appears that many of the intracellular effects of schweinfurthins are due to, or impacted by, the effect of schweinfurthins on lipid metabolism, synthesis, and homeostasis. These effects include impaired trafficking from the trans‐golgi network, disruption of lipid rafts, changes in oxysterol‐binding protein activity, and interference with the isoprenoid biosynthesis pathway (IBP). Cancer cells are known to rely heavily on fatty acid, lipid, and sterol synthesis for growth and proliferation. Therefore, compounds that target these needs, such as schweinfurthins, display promise as novel therapeutics. This timely review will take an in‐depth look at the history of schweinfurthins, their synthesis, where the research presently stands, and the questions that remain.Keywords
This publication has 108 references indexed in Scilit:
- The Cancer Genome Atlas Pan-Cancer analysis projectNature Genetics, 2013
- Lipid raft: A floating island of death or survivalToxicology and Applied Pharmacology, 2012
- Relevance of the C-5 position to schweinfurthin induced cytotoxicityBioorganic & Medicinal Chemistry, 2011
- Membrane-trafficking sorting hubs: cooperation between PI4P and small GTPases at the trans-Golgi networkTrends in Cell Biology, 2011
- Natural products reveal cancer cell dependence on oxysterol-binding proteinsNature Chemical Biology, 2011
- Exploration of Cascade Cyclizations Terminated by Tandem Aromatic Substitution: Total Synthesis of (+)-Schweinfurthin AThe Journal of Organic Chemistry, 2011
- A role for oxysterol-binding protein–related protein 5 in endosomal cholesterol traffickingJournal of Cell Biology, 2011
- Inhibition of Golgi Apparatus Glycosylation Causes Endoplasmic Reticulum Stress and Decreased Protein SynthesisJournal of Biological Chemistry, 2010
- Schweinfurthins I and J from Macaranga schweinfurthiiJournal of Natural Products, 2009
- Antiproliferative Prenylated Stilbenes and Flavonoids from Macaranga alnifolia from the Madagascar Rainforest,1Journal of Natural Products, 2007