Related Experiment Video

Updated: Feb 22, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

11.6K

Disrupting CCT-β : β-tubulin selectively kills CCT-β overexpressed cancer cells through MAPKs activation

Yan-Jin Liu1, Vathan Kumar1, Yuan-Feng Lin2

  • 1Institute of Biological Chemistry, Academia Sinica, Taipei 11529, Taiwan, ROC.

Cell Death & Disease
|September 15, 2017
PubMed

Insights

The compound I-Trp effectively targets cancer cells overexpressing chaperonin-containing TCP-1β (CCT-β) by disrupting the CCT-β:β-tubulin complex, leading to apoptosis. This approach shows promise for treating various cancers, including triple-negative breast, colorectal, and gastric cancers.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Drug Discovery

Background:

  • Chaperonin-containing TCP-1β (CCT-β) plays a role in protein folding and is overexpressed in certain cancers.
  • The compound I-Trp has previously shown potential in disrupting the CCT-β:β-tubulin interaction, leading to apoptosis.

Purpose of the Study:

  • To screen cancer cell lines for CCT-β overexpression and evaluate the efficacy of I-Trp.
  • To synthesize and assess analogs of I-Trp for improved cytotoxicity.
  • To elucidate the apoptotic mechanisms induced by I-Trp.

Main Methods:

  • Screening of various cancer cell lines for CCT-β expression levels.
  • Cytotoxicity assays using I-Trp and its synthesized analogs.
  • Apoptosis mechanism investigations, including protein ubiquitination/degradation and ER-associated protein degradation pathways.
  • MAPK pathway activation analysis.

Main Results:

  • CCT-β overexpression was identified in MDA-MB-231 (triple-negative breast cancer), Colo205 and HCT116 (colorectal cancer), and MKN-45 (gastric cancer) cell lines.
  • I-Trp demonstrated potent cytotoxicity (sub- to low-μM EC50) against these CCT-β overexpressing cancer cells, while sparing normal cells (MCF-10A).
  • Apoptosis was induced via activation of protein ubiquitination/degradation and ER-associated protein degradation pathways, triggered by MAPK activation following CCT-β:β-tubulin complex disruption.

Conclusions:

  • Disrupting the CCT-β:β-tubulin complex is a viable therapeutic strategy for CCT-β overexpressing cancers.
  • I-Trp and its analogs represent promising drug candidates for targeted cancer therapy.
  • The study establishes a mechanistic link between CCT-β:β-tubulin disruption, MAPK activation, and downstream apoptotic pathways.

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
Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies07:47

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies

Published on: September 15, 2023

2.3K

Related Concept Videos

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...
6.1K
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...
9.0K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.1K
Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
6.0K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
8.8K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.8K