Related Experiment Video

Updated: May 24, 2026

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer
09:24

3-D Cell Culture System for Studying Invasion and Evaluating Therapeutics in Bladder Cancer

Published on: September 13, 2018

Celastrol decreases specificity proteins (Sp) and fibroblast growth factor receptor-3 (FGFR3) in bladder cancer cells

Gayathri Chadalapaka1, Indira Jutooru, Stephen Safe

  • 1Department of Veterinary Physiology and Pharmacology, Texas A&M University, 4466 TAMU, Vet Res Bldg 410, College Station, TX 77843, USA.

Carcinogenesis
|February 16, 2012
PubMed

Insights

Celastrol (CSL) demonstrates anticancer effects by inhibiting bladder cancer cell growth and migration. Its mechanism involves reducing specificity protein (Sp) transcription factors, crucial for tumor progression.

Area of Science:

  • Molecular Biology
  • Oncology
  • Natural Products Chemistry

Background:

  • Celastrol (CSL) is a natural triterpenoid with documented anticancer properties.
  • Bladder cancer progression is often linked to the activity of specificity protein (Sp) transcription factors.
  • Fibroblast growth factor receptor-3 (FGFR3) is a potential therapeutic target in bladder cancer.

Purpose of the Study:

  • To investigate the anticancer mechanisms of Celastrol (CSL) in bladder cancer cells.
  • To elucidate the role of specificity protein (Sp) transcription factors in CSL's anti-bladder cancer effects.
  • To characterize the pathways involved in CSL-mediated downregulation of Sp factors.

Main Methods:

  • Cell viability, migration, and colony formation assays were performed on KU7 and 253JB-V bladder cancer cell lines.
  • Western blotting and quantitative PCR were used to assess the expression of Sp transcription factors and related genes.
  • Reactive oxygen species (ROS) generation and proteasome activity were analyzed.
  • MicroRNA (miRNA) expression levels (miR-27a, miR-20a/17-5p) and Sp repressor expression (ZBTB4, ZBTB10) were investigated.

Main Results:

  • CSL inhibited bladder cancer cell proliferation, migration, and colony formation in vitro and reduced tumor growth in vivo.
  • CSL downregulated Sp1, Sp3, and Sp4 transcription factors and their target genes (VEGF, survivin, cyclin D1, FGFR3).
  • The mechanism of Sp downregulation was cell-context dependent, involving proteasome-dependent and -independent pathways.
  • In 253JB-V cells, CSL-induced ROS generation was critical for growth inhibition and Sp factor repression.
  • CSL increased ROS, leading to the induction of Sp repressors ZBTB4/ZBTB10 via downregulation of miR-27a and miR-20a/17-5p.

Conclusions:

  • Celastrol exhibits significant anticancer activity against bladder cancer by targeting Sp transcription factors.
  • The anticancer effects of CSL in 253JB-V cells are mediated by ROS induction, which upregulates Sp repressors through miRNA modulation.
  • CSL represents a promising therapeutic agent for bladder cancer, potentially by disrupting Sp-driven oncogenic pathways.

More Related Videos

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth06:35

A Mouse Model to Investigate the Role of Cancer-Associated Fibroblasts in Tumor Growth

Published on: December 22, 2020

Related Concept Videos

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...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...