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Met receptor inhibitor SU11274 localizes in the endoplasmic reticulum

Edwin J Wiest1, Heather Jensen Smith2, Michael A Hollingsworth1

  • 1Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute, Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.

Biochemical and Biophysical Research Communications
|May 13, 2018
PubMed

Insights

SU11274, a c-Met inhibitor, fluoresces and accumulates in specific cell parts. This study found it primarily targets the endoplasmic reticulum in human pancreatic cancer cells.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Pharmacology

Background:

  • SU11274 is a known class I c-Met inhibitor with anti-cancer properties.
  • The drug exhibits unique fluorescent properties when exposed to 488 nm laser light.
  • Understanding drug localization is crucial for cancer therapy optimization.

Purpose of the Study:

  • To investigate the subcellular localization and accumulation patterns of SU11274.
  • To identify specific organelles targeted by SU11274 in human pancreatic cancer cells.
  • To leverage the fluorescent properties of SU11274 for intracellular tracking.

Main Methods:

  • Utilizing the intrinsic fluorescence of SU11274.
  • Employing laser excitation at 488 nm.
  • Microscopy techniques to observe intracellular distribution in pancreatic cancer cells.

Main Results:

  • SU11274 demonstrated rapid and specific accumulation within cells.
  • The drug's fluorescent properties facilitated visualization of its intracellular trafficking.
  • Predominant accumulation of SU11274 was observed in the endoplasmic reticulum.

Conclusions:

  • SU11274 is rapidly trafficked and predominantly accumulates in the endoplasmic reticulum.
  • The endoplasmic reticulum is a key organelle for SU11274 localization in pancreatic cancer.
  • These findings provide insights into the pharmacodynamics of SU11274.
Keywords:
Endoplasmic reticulumSU11274Sulfonylurea receptorUnfolded protein response

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