Related Experiment Video

Updated: Aug 16, 2026

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages
06:47

Experimental Analysis of Apoptotic Thymocyte Engulfment by Macrophages

Published on: May 24, 2019

A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid

Shailaja Kasibhatla1, Katayoun A Jessen, Sergei Maliartchouk

  • 1Maxim Pharmaceuticals, Inc., 6650 Nancy Ridge Drive, San Diego, CA 92121, USA. skasibhatla@maxim.com

Proceedings of the National Academy of Sciences of the United States of America
|August 17, 2005
PubMed

Insights

Gambogic acid (GA) targets the transferrin receptor (TfR), which is overexpressed in cancers. GA binding to TfR triggers rapid apoptosis in tumor cells, suggesting a new cancer therapy approach.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Transferrin receptor (TfR) is frequently overexpressed in various cancer types.
  • Gambogic acid (GA), a compound from traditional Chinese medicine, has shown potential anti-cancer properties.

Purpose of the Study:

  • To investigate TfR as a molecular target for gambogic acid (GA).
  • To elucidate the mechanism by which GA induces apoptosis in cancer cells via TfR.

Main Methods:

  • Investigated GA binding to TfR, including its binding site.
  • Utilized RNA interference to down-regulate TfR expression.
  • Assessed the impact of TfR down-regulation on GA-induced apoptosis.

Main Results:

  • Identified TfR as a direct target of GA, with a distinct binding site.
  • GA binding to TfR inhibits receptor internalization.
  • Down-regulation of TfR significantly reduced sensitivity to GA-induced apoptosis.
  • GA binding to TfR triggers a specific signaling pathway leading to rapid tumor cell apoptosis.

Conclusions:

  • Transferrin receptor (TfR) is a primary receptor for gambogic acid (GA).
  • GA binding to TfR induces rapid apoptosis in cancer cells.
  • GA represents a novel therapeutic strategy for targeting TfR in cancer treatment.

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

Related Concept Videos

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...
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...