Related Experiment Video

Updated: Oct 31, 2025

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

1.8K

Celastrol Modulates Multiple Signaling Pathways to Inhibit Proliferation of Pancreatic Cancer via DDIT3 and ATF3

Mahmoud Youns1,2, Momen Askoura3, Hisham A Abbas3

  • 1Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo, Egypt.

Oncotargets and Therapy
|July 1, 2021
PubMed
Abstract

Insights

Celastrol, a natural compound, effectively inhibits pancreatic cancer cell growth and induces apoptosis. Its antitumor effects are linked to specific gene expression changes, offering a potential therapeutic avenue.

Area of Science:

  • Oncology
  • Molecular Biology
  • Natural Products Chemistry

Background:

  • Pancreatic cancer presents a significant global health challenge with increasing incidence.
  • Celastrol, a natural product, exhibits known anti-inflammatory, anti-angiogenic, and antioxidant properties.

Purpose of the Study:

  • To investigate the antitumor effects of celastrol on pancreatic cancer cells.
  • To explore celastrol's influence on global gene expression in pancreatic cancer.

Main Methods:

  • Sulforhodamine B assay for antiproliferative activity.
  • Apoptosis assays (caspase 3/7, DNA fragmentation) and prostaglandin E2 (PGE2) inhibition assessment.
  • Microarray gene expression profiling to identify key regulatory genes.

Main Results:

  • Celastrol demonstrated suppression of pancreatic cancer cell growth and induced apoptosis.
  • Celastrol inhibited PGE2 production.
  • Gene expression analysis revealed celastrol's cytotoxic effect mediated by ATF3 and DDIT3 overexpression, and RRM2 and MCM4 downregulation.

Conclusions:

  • Celastrol shows promise as an agent to prevent pancreatic cancer growth.
  • The study identifies key regulatory genes (ATF3, DDIT3, RRM2, MCM4) modulated by celastrol.
  • Further research is warranted to fully elucidate celastrol's mechanisms for pancreatic cancer treatment.
Keywords:
DDIT3MCM4RRM2celastrolnatural productspancreatic cancer

More Related Videos

Author Spotlight: Validating Cancer Therapy Responses with Desmoplastic Spheroid Models03:42

Author Spotlight: Validating Cancer Therapy Responses with Desmoplastic Spheroid Models

Published on: September 27, 2024

1.7K
Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

19.8K

Related Concept Videos

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...
4.0K
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.7K
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...
5.1K
Cell Specific Gene Expression01:58

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
14.4K