Related Experiment Video

Updated: Jul 4, 2025

Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
07:59

Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma

Published on: September 3, 2021

6.4K

CP-673451, a Selective Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitor, Induces Apoptosis in

Jinchutha Duangdara1, Boonyakorn Boonsri1,2, Apinya Sayinta1,3

  • 1Department of Anatomy, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Pharmaceuticals (Basel, Switzerland)
|January 26, 2024
PubMed

Insights

Platelet-derived growth factor receptor (PDGFR) inhibitors like CP-673451 show promise for treating Opisthorchis viverrini-related cholangiocarcinoma (CCA). This drug induces cancer cell death by disrupting key survival pathways and increasing oxidative stress.

Area of Science:

  • Oncology
  • Molecular Biology
  • Parasitology

Background:

  • Platelet-derived growth factors (PDGFs) and their receptors (PDGFRs) are crucial for cholangiocarcinoma (CCA) cell survival via tumor-stroma interactions.
  • Previous clinical trials of PDGFR inhibitors in CCA showed limited efficacy, necessitating further investigation, especially in Opisthorchis viverrini (OV)-associated cases.

Purpose of the Study:

  • To investigate the effect of PDGFR inhibitors on OV-related CCA cells.
  • To elucidate the molecular mechanisms underlying PDGFR inhibitor action in CCA.

Main Methods:

  • Analysis of PDGF and PDGFR mRNA expression in CCA tissues.
  • Assessment of PDGFR-α and PDGFR-β expression in CCA cells and cancer-associated fibroblasts (CAFs).
  • Evaluation of the selective PDGFR inhibitor CP-673451's effects on CCA cell viability and molecular pathways.

Main Results:

  • PDGF and PDGFR mRNAs were overexpressed in CCA tissues.
  • PDGFR-α was highly expressed in CCA cells, while PDGFR-β was predominantly in CAFs.
  • CP-673451 induced CCA cell death by inhibiting the PI3K/Akt/Nrf2 pathway, reducing antioxidant gene expression, increasing ROS levels, and promoting apoptosis.

Conclusions:

  • CP-673451 demonstrates potential as a therapeutic agent for CCA, particularly OV-related CCA.
  • The drug's mechanism involves suppressing the PI3K/Akt/Nrf2 pathway, leading to oxidative stress and apoptosis.
  • Further clinical investigation of CP-673451 for CCA treatment is warranted.
Keywords:
CP-673451Nrf2Opisthorchis viverriniPDGFR inhibitorcholangiocarcinoma

More Related Videos

Production and Detection of Reactive Oxygen Species ROS in Cancers07:17

Production and Detection of Reactive Oxygen Species ROS in Cancers

Published on: November 21, 2011

70.1K
Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma13:18

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

Published on: March 3, 2023

1.3K

Related Concept Videos

Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
7.7K
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...
7.6K
NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
7.4K
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...
3.8K
Rous Sarcoma Virus (RSV) and Cancer01:03

Rous Sarcoma Virus (RSV) and Cancer

Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand  RNA genome. Its genome consists of four main open...
5.1K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
13.4K