Related Experiment Video

Updated: Aug 17, 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

Tyrphostin induces non-apoptotic programmed cell death in colon tumor cells

B Szende1, G Kéri, Z Szegedi

  • 11st Institute of Pathology and Experimental Cancer Research, Hungarian Academy of Sciences, Semmelweis University of Medicine, Budapest, Hungary.

Cell Biology International
|November 1, 1995
PubMed

Insights

The tyrosine kinase inhibitor AG213 selectively induces programmed cell death in colon tumor cells. This novel cell death pathway, distinct from apoptosis, offers a potential new strategy for targeted cancer therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors are crucial in cancer therapy.
  • Understanding diverse programmed cell death mechanisms is vital for developing targeted treatments.

Purpose of the Study:

  • To investigate the in vitro effects of the EGFR tyrosine kinase inhibitor AG213 on HT-29 human colon tumor cells.
  • To characterize the type of programmed cell death induced by AG213.

Main Methods:

  • In vitro cell culture of HT-29 human colon tumor cells.
  • Treatment with varying concentrations of AG213 (45-450 microM).
  • Morphological analysis and biochemical assays (acid phosphatase activity) to determine cell death mechanisms.

Main Results:

  • AG213 effectively blocked HT-29 cell proliferation.
  • Morphological and biochemical data indicated AG213 induces Clarke III type programmed cell death, characterized by non-lysosomal vesiculation.
  • Protein and RNA synthesis inhibition (using Cycloheximide and Actinomycin-D) reduced AG213's effect.
  • Acid phosphatase activity was observed in the Golgi and vacuoles post-treatment.

Conclusions:

  • The selective tyrosine kinase inhibitor AG213 induces a unique form of programmed cell death (Clarke III) in colon tumor cells.
  • This mechanism differs from apoptosis induced by non-selective tyrosine kinase inhibitors.
  • Targeting this specific cell death pathway presents a potential new therapeutic strategy for selective tumor cell killing.

More Related Videos

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Quantification of Cytokine-Induced Cell Death in Human Colonic Organoids Using Live Fluorescence Microscopy10:03

Quantification of Cytokine-Induced Cell Death in Human Colonic Organoids Using Live Fluorescence Microscopy

Published on: August 2, 2024

Related Concept Videos

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...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
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...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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...
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...