Protoporphyrin IX

About: Protoporphyrin IX is a research topic. Over the lifetime, 2250 publications have been published within this topic receiving 65544 citations. The topic is also known as: PpIX.

ALA- and ALA-hexylester-induced protoporphyrin IX fluorescence and distribution in multicell tumour spheroids

Abstract: Synthesis of protoporphyrin IX (PpIX) in intact murine mammary cancer cell spheroids is reported from optical sections obtained using a laser scanning confocal fluorescence microscope. EMT6 spheroids 275–350 μ m in diameter were incubated in 0.1–15 mM aminolevulinic acid (ALA) or 0.001–2 mM ALA-hexylester (h-ALA) to test the ability of both pro-drugs to diffuse into the spheroids and induce PpIX production. Spheroids incubated with ALA show significant fluorescence nonuniformity for all concentrations, with the outermost cells exhibiting greater porphyrin fluorescence. Comparable levels of fluorescence throughout the optical section are achieved with approximately 100-fold lower h-ALA concentrations, indicating that the interior cells maintain esterase activity and porphyrin synthesis and that h-ALA diffuses efficiently to the spheroid interior. Fluorescence gradients are less pronounced with h-ALA incubation, in part because of apparent saturation of esterase activity in the spheroid perimeter. Proliferating (Ki67 positive) and quiescent cell populations exhibit remarkably different h-ALA concentration dependencies. The incubation concentration resulting in maximum fluorescence with ALA is 10 mM, while the optimal concentration for h-ALA is 200-fold lower at 0.05 mM. Exceeding these optimal concentrations for both pro-drugs leads to an overall loss of fluorescence. © 2001 Cancer Research Campaign http://www.bjcancer.com

Photodynamic therapy and topical aminolevulinic acid: an overview.

Abstract: Photodynamic therapy is a non-invasive technique used in the treatment of skin diseases which has various advantages, one being the ability to localize treatment to the area being treated, which is common among most photosensitizers. Aminolevulinic acid is a prodrug that is metabolized intracellularly to form the photosensitizing molecule protoporphyrin IX (PpIX). When PpIX is activated by light, cytotoxic reactive oxygen species and free radicals are generated. This phototoxic effect may cause malignant and non-malignant hyperproliferative tissue to be destroyed, to decrease in size, and to eventually disappear. The application of topical aminolevulinic acid 20% followed by the use of a blue light photodynamic therapy illuminator is indicated in the US for the treatment of non-hyperkeratotic actinic keratoses of the face or scalp. There are data suggesting that aminolevulinic acid/photodynamic therapy may also be beneficial in acne vulgaris, verrucae, psoriasis, mycosis fungoides, and human papillomavirus. This treatment modality has also proven effective in the management of skin cancer such as, Bowen disease and basal cell carcinoma. Further experience in the use of photodynamic therapy will help define its utility in the management of actinic keratosis and other dermatoses.

Dormant cancer cells accumulate high protoporphyrin IX levels and are sensitive to 5-aminolevulinic acid-based photodynamic therapy.

Abstract: Photodynamic therapy (PDT) and diagnosis (PDD) using 5-aminolevulinic acid (ALA) to drive the production of an intracellular photosensitizer, protoporphyrin IX (PpIX), are in common clinical use. However, the tendency to accumulate PpIX is not well understood. Patients with cancer can develop recurrent metastatic disease with latency periods. This pause can be explained by cancer dormancy. Here we created uniformly sized PC-3 prostate cancer spheroids using a 3D culture plate (EZSPHERE). We demonstrated that cancer cells exhibited dormancy in a cell density-dependent manner not only in spheroids but also in 2D culture. Dormant cancer cells accumulated high PpIX levels and were sensitive to ALA-PDT. In dormant cancer cells, transporter expressions of PEPT1, ALA importer, and ABCB6, an intermediate porphyrin transporter, were upregulated and that of ABCG2, a PpIX exporter, was downregulated. PpIX accumulation and ALA-PDT cytotoxicity were enhanced by G0/G1-phase arrestors in non-dormant cancer cells. Our results demonstrate that ALA-PDT would be an effective approach for dormant cancer cells and can be enhanced by combining with a cell-growth inhibitor.

On the basis for tumor selectivity in the 5‐aminolevulinic acid‐induced synthesis of protoporphyrin IX

Abstract: When 5-aminolevulinic acid (ALA) is administered topically, intravenously or intraperitoneally to tumor-bearing animals or humans, tumor selective production of protoporphyrin IX (PpIX) is frequent...