Related Experiment Video

Updated: Feb 17, 2026

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
10:50

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons

Published on: April 24, 2021

1.4K

Celastrol induces apoptosis in hepatocellular carcinoma cells via targeting ER-stress/UPR

Bo Ren1, Hui Liu2, Hang Gao1

  • 1The Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun 130021, China.

Oncotarget
|December 2, 2017
PubMed

Insights

Celastrol, a compound from traditional Chinese medicine, shows promise for treating hepatocellular carcinoma (HCC). It inhibits cancer cell proliferation and tumor growth by inducing endoplasmic reticulum (ER) stress and the unfolded protein response (UPR).

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) presents significant global health challenges with limited therapeutic options.
  • Endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) are critical in cell fate regulation and emerging as targets for anticancer drug development.
  • Celastrol, a natural compound, exhibits anti-tumor properties, with prior research indicating UPR induction in various cancers.

Purpose of the Study:

  • To investigate the role of ER stress and UPR in hepatocellular carcinoma (HCC) response to celastrol.
  • To elucidate the mechanisms by which celastrol affects HCC cell proliferation and tumor growth.
  • To evaluate celastrol as a potential therapeutic agent for HCC.

Main Methods:

  • Cell proliferation assays and cell cycle analysis in HepG2 and Bel7402 HCC cell lines treated with celastrol.
  • Assessment of apoptosis, ER stress markers, and UPR activation following celastrol exposure.
  • Evaluation of celastrol's anti-tumor efficacy in a murine syngeneic H22 tumor model.

Main Results:

  • Celastrol treatment led to G2/M cell cycle arrest and inhibited proliferation in HCC cell lines.
  • Celastrol induced apoptosis through the activation of the intrinsic apoptotic pathway, mediated by ER stress and UPR.
  • In vivo studies demonstrated that celastrol suppressed H22 tumor growth by promoting ER stress and apoptosis.

Conclusions:

  • Celastrol effectively inhibits HCC cell proliferation and tumor growth.
  • The anti-cancer effects of celastrol in HCC are linked to the induction of ER stress and UPR, leading to apoptosis.
  • Celastrol represents a potential therapeutic candidate for HCC, targeting the ER-stress/UPR pathway.
Keywords:
ER stressapoptosisautophagycelastrolhepatocellular carcinoma

More Related Videos

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

19.2K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
8.7K
The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.5K
Role of ER in the Secretory Pathway01:17

Role of ER in the Secretory Pathway

Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
7.3K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K