Related Experiment Video

Updated: Mar 18, 2026

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery
07:20

A Novel Stromal Fibroblast-Modulated 3D Tumor Spheroid Model for Studying Tumor-Stroma Interaction and Drug Discovery

Published on: February 28, 2020

10.5K

Fatostatin Inhibits Cancer Cell Proliferation by Affecting Mitotic Microtubule Spindle Assembly and Cell Division

Ankur A Gholkar1, Keith Cheung1, Kevin J Williams2

  • 1From the Departments of Chemistry and Biochemistry.

The Journal of Biological Chemistry
|July 6, 2016
PubMed

Insights

Fatostatin, an inhibitor of sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), not only affects lipid metabolism but also inhibits cancer cell division. This dual action suggests potential for treating aggressive cancers like glioblastomas.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Sterol regulatory element-binding protein (SREBP) transcription factors are crucial for lipid and cholesterol metabolism, making them targets for metabolic diseases and cancer therapy.
  • Fatostatin is a specific inhibitor of SREBP cleavage-activating protein (SCAP), impacting SREBP activation and exhibiting antitumor properties.

Purpose of the Study:

  • To investigate the anticancer mechanisms of Fatostatin, specifically its effects on cell division beyond SREBP inhibition.
  • To compare the antimitotic effects of Fatostatin with other SREBP inhibitors like PF-429242 and Betulin.

Main Methods:

  • Analysis of the cell cycle effects of Fatostatin, PF-429242, and Betulin.
  • Assessment of Fatostatin's impact on tubulin polymerization, mitotic arrest, spindle assembly checkpoint, and mitotic catastrophe.

Main Results:

  • Fatostatin demonstrated significant antimitotic properties, unlike PF-429242 and Betulin.
  • Fatostatin inhibited tubulin polymerization, induced mitotic arrest, activated the spindle assembly checkpoint, and led to mitotic catastrophe and reduced cell viability.
  • These effects were observed in cancer cells, suggesting a direct impact on cell division.

Conclusions:

  • Fatostatin's anticancer efficacy is attributed to both its inhibition of SREBP-mediated lipid metabolism and its direct antimitotic activity.
  • The dual mechanism of Fatostatin holds promise for treating aggressive cancers with high lipid metabolism and proliferation rates, such as glioblastomas.
  • Fatostatin's ability to disrupt cell division offers a novel therapeutic strategy for cancers resistant to current treatments.
Keywords:
BetulinFatostatinPF-429242SREBPcancercell deathcell divisionlipid metabolismmitosis

More Related Videos

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.6K
Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module10:39

Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module

Published on: June 18, 2015

13.9K

Related Concept Videos

Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.2K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.1K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
3.8K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
9.1K