by A recent study conducted in Japan has shed light on a novel mechanism by which cancer cells can be selectively destroyed using photodynamic therapy (PDT). Cancer has been the leading cause of death in Japan since 1981, and while surgery, chemotherapy, and radiotherapy are the main treatment options, they often have significant impacts on postoperative quality of life. Therefore, the development of new treatment methods is highly desired.
PDT is an emerging treatment method that has gained attention due to its less invasive nature compared to traditional therapies. The process involves injecting a photosensitizer into the body, followed by exposing the diseased area to light. This light exposure induces a photochemical reaction in the photosensitizer, leading to the generation of reactive oxygen species (ROS) that destroy the cancer cells.
To improve the effectiveness of PDT, researchers sought to understand how light-sensitive substances specifically accumulate in cells and how ROS efficiently target and kill cancer cells. The study focused on a newly developed photosensitizer called polphylipoprotein (PLP), known for its high therapeutic efficacy. However, the underlying mechanisms of PLP’s effectiveness had remained uncleara.
Using confocal superresolution microscopy, the research team investigated the effects of PDT with PLP on two cell lines: the normal rat gastric epithelial cell line RGM1 and a gastric mucosa-derived cancer-like mutant RGK1 (a cancer cell of the same origin).
The results of the study, published in Communications Biology, demonstrated that PLP accumulates in the membranes of intracellular vesicles called phagosomes. These vesicles are produced early in the autophagy mechanism, which is responsible for degrading and reusing foreign substances and proteins within the cell.
The study revealed that when cancer cells, which are rapidly proliferating, are starved, the autophagy mechanism is activated. After PDT treatment with PLP, the membranes of phagosomes in the cancer cells ruptured, releasing hydrolytic enzymes and ROS, along with the breakdown products of cytoplasmic components such as proteins, lipids, mitochondria, and endoplasmic reticulum. These substances diffused into the cell, resulting in necrosis. In contrast, in the normal cell line RGM1, small phagosomes merged together to form larger phagosomes without rupturing.
This phenomenon highlights a unique and novel mechanism by which PLP selectively induces necrosis in cancer cells through the manipulation of the autophagy mechanism under starvation conditions. This discovery opens up new possibilities for the development of cancer therapies, particularly in terms of the high selectivity and potential efficacy of PLP-PDT.
The findings of this study provide valuable insights into the underlying mechanisms of PDT and shed light on how to improve its effectiveness and selectivity. By understanding how to specifically target cancer cells and exploit their own autophagy processes, researchers can develop more effective and efficient treatment methods for cancer patients. The use of PLP as a photosensitizer shows promise in this regard, and further research is warranted to explore its full potential in clinical applications. Overall, these findings represent a significant step forward in the field of cancer therapy development.
