Related Experiment Video

Updated: Jul 11, 2026

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
19:44

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

TAE226-induced apoptosis in breast cancer cells with overexpressed Src or EGFR

Vita M Golubovskaya1, Christopher Virnig, William G Cance

  • 1Department of Surgery, University of Florida, Gainesville, Florida, USA.

Molecular Carcinogenesis
|September 13, 2007
PubMed

Insights

A novel drug, TAE226, effectively induces apoptosis in breast cancer cells by inhibiting focal adhesion kinase (FAK). This FAK inhibitor shows promise for treating breast cancer, even in cells resistant to other FAK-targeting therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase overexpressed in human tumors, regulating cell adhesion and survival.
  • Previous studies showed dominant-negative FAK (FAK-CD) induces apoptosis in breast cancer cells, an effect suppressed by Src or EGFR overexpression.
  • Activated Src tyrosine kinase and epidermal growth factor receptor (EGFR) can interfere with FAK-mediated apoptosis.

Purpose of the Study:

  • To investigate the efficacy of a novel FAK inhibitor, TAE226, in inducing apoptosis in breast cancer cell lines.
  • To compare the effects of TAE226 with a dominant-negative FAK inhibitor (Ad-FAK-CD).
  • To assess the sensitivity of breast cancer cells overexpressing Src or EGFR to TAE226 treatment.

Main Methods:

  • Utilized stable breast cancer cell lines overexpressing Src or EGFR, alongside control cell lines.
  • Treated cell lines with varying doses of TAE226 and analyzed detachment and apoptosis.
  • Compared TAE226 effects with those of adenoviral FAK-CD (Ad-FAK-CD).
  • Assessed protein levels of Y397-FAK, FAK, PARP, and caspase-3.

Main Results:

  • TAE226 induced a dose-dependent increase in detachment and apoptosis in multiple breast cancer cell lines.
  • TAE226 treatment led to downregulation of Y397-FAK and FAK, and activation of PARP and caspase-3.
  • Cells overexpressing Src or EGFR were not resistant to TAE226, unlike their resistance to Ad-FAK-CD.
  • Normal breast MCF-10A cells were resistant to both TAE226 and Ad-FAK-CD.

Conclusions:

  • TAE226 effectively inhibits FAK autophosphorylation at 10-20 microM, inducing apoptosis in breast cancer cells.
  • TAE226 is effective in breast cancer cells resistant to Ad-FAK-CD.
  • TAE226 demonstrates potential as a therapeutic agent for breast cancer treatment.

More Related Videos

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration11:13

Exploring the Pharmacological Action and Molecular Mechanism of Salidroside in Inhibiting MCF-7 Cell Proliferation and Migration

Published on: June 9, 2023

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
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...
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...