Related Experiment Video

Updated: Aug 22, 2026

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies
07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

Effect on tumor cells of blocking survival response to glucose deprivation

Hae-Ryong Park1, Akihiro Tomida, Shigeo Sato

  • 1Laboratory of Chemical Biology, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.

Journal of the National Cancer Institute
|September 2, 2004
PubMed
Abstract

Insights

Versipelostatin (VST) selectively kills glucose-deprived cancer cells by inhibiting the unfolded protein response (UPR). This novel compound also inhibited tumor growth in vivo, suggesting a new therapeutic strategy for solid tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Solid tumors often experience glucose deprivation, activating the unfolded protein response (UPR) in cancer cells.
  • The novel macrocyclic compound versipelostatin (VST) inhibits transcription of GRP78, a key UPR-activated gene.

Purpose of the Study:

  • To investigate the effect of VST on UPR induced by glucose deprivation and other stressors.
  • To evaluate VST's impact on tumor growth in vivo.

Main Methods:

  • Cell culture models (HT-29, HT1080, MKN74) under glucose deprivation or chemical stress.
  • Analysis of UPR target genes (GRP78, GRP94) and transcriptional activators (ATF6, XBP1, ATF4) via RT-PCR and immunoblotting.
  • In vivo assessment of VST's antitumor activity in an MKN74 xenograft model.

Main Results:

  • VST inhibited UPR target genes and UPR activators (XBP1, ATF4) specifically under glucose deprivation.
  • VST selectively induced massive cell death in glucose-deprived cells.
  • VST demonstrated statistically significant inhibition of tumor growth, both alone and in combination with cisplatin.

Conclusions:

  • Disrupting the UPR presents a novel therapeutic strategy for targeting glucose-deprived solid tumors.
  • VST shows promise as a targeted therapy for cancers experiencing metabolic stress.

More Related Videos

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures07:48

Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures

Published on: December 26, 2016

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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 specific...
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...