Singlet Oxygen, Photodynamic Therapy, and Mechanisms of Cancer Cell Death

Photodynamic therapy (PDT) can be developed into an important arsenal against cancer; it is a minimally invasive therapy, which is used in the treatment or/and palliation of a variety of cancers and benign diseases. The removal of cancerous tissue is achieved with the use of photosensitizer and a light source, which excites the photosensitizer. This excitation causes the photosensitizer to generate singlet oxygen and other reactive oxygen species. PDT has been used in several types of cancers including nonmelanoma skin cancer, bladder cancer, esophageal cancer, head and neck cancer, and non-small cell lung cancer (NSCLC). Although it is routinely used in nonmelanoma skin cancer, it has not been widely adopted in other solid cancers due to a lack of clinical data showing the superiority of PDT over other forms of treatment. Singlet oxygen used in PDT can alter the activity of the catalase, which induces immunomodulation through HOCl signaling. The singlet oxygen can induce apoptosis through both the extrinsic and intrinsic pathways. The extrinsic pathway of apoptosis starts with the activation of the Fas receptor by singlet oxygen that leads to activation of the caspase-7 and caspase-3. In the case of the intrinsic pathway, disruption caused by singlet oxygen in the mitochondria membrane leads to the release of cytochrome c, which binds with APAF-1 and procaspase-9, forming a complex, which activates caspase-3. Mechanisms of PDT action can vary according to organelles affected. In the plasma membrane, membrane disruption is caused by the oxidative stress leading to the intake of calcium ions, which causes swelling and rupture of cells due to excess intake of water, whereas disruption of lysosome causes the release of the cathepsins B and D, which cleave Bid into tBid, which changes the mitochondrial outer membrane permeability (MOMP). Oxidative stress causes misfolding of protein in the endoplasmic reticulum. When misfolding exceeds the threshold, it triggers unfolding protein response (UPR), which leads to activation of caspase-9 and caspase-3. Finally, the activation of p38 MAPK works as an alternative pathway for the induction of MOMP.

Automated summary

Photodynamic therapy (PDT) is a minimally invasive therapy that uses photosensitizers and light sources to remove cancerous tissue. It can be used in the treatment of various types of cancers and induces cell apoptosis by altering the function of organelles.