Apoptin enhances radiation-induced cell death in poorly responding head and neck squamous cell carcinoma cells

Remilio A L Schoop1, Elizabeth M E Verdegaal, Robert J Baatenburg de Jong

  • 1Department of Otolaryngology, Head and Neck Surgery, Leiden University Medical Center, Leiden, the Netherlands.

Insights

Chicken anaemia virus-derived apoptin protein enhances radiotherapy for head and neck cancers. This protein sensitizes radioresistant tumors, increasing cell death when combined with irradiation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Head and neck cancer treatment outcomes remain poor, necessitating novel therapeutic strategies.
  • Radiotherapy resistance in tumors is a significant clinical challenge.
  • Combining irradiation with apoptosis-inducing agents is a promising approach to sensitize radioresistant tumors.

Purpose of the Study:

  • To investigate the efficacy of chicken anaemia virus-derived apoptin in combination with irradiation for human head and neck squamous carcinoma cell lines.
  • To determine if apoptin can sensitize radioresistant cancer cells to irradiation-induced apoptosis.

Main Methods:

  • Utilized radiosensitive SCC61 and radioresistant SQD9 human head and neck squamous carcinoma cell lines.
  • Administered concurrent irradiation and apoptin treatment.
  • Assessed mitochondrial cytochrome c release and caspase-3 cleavage as markers of apoptosis.
  • Evaluated cell death using a colony survival assay.

Main Results:

  • Concurrent irradiation and apoptin treatment induced mitochondrial cytochrome c release and caspase-3 cleavage in both cell lines.
  • Irradiation alone did not induce these apoptosis markers in radioresistant SQD9 cells.
  • Combined apoptin and irradiation significantly increased cell death, particularly in radioresistant SQD9 cells, compared to irradiation alone.

Conclusions:

  • Apoptin treatment effectively enhances radiotherapy outcomes for head and neck cancers.
  • Apoptin shows particular promise in overcoming radioresistance in squamous cell carcinomas.
  • This strategy offers a potential new therapeutic option for patients with poorly responding tumors.

Related Concept Videos

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...
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...
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.
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...
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.
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...