Effect of (R)L-sulforaphane on 5-aminolevulinic acid-mediated photodynamic therapy

Abstract

Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or so-called ALA-PDT, is a standard procedure in the clinical practice. For optimal treatment of nonmelanoma skin cancer, actinic keratoses and other dermatoses improvements are required because of adverse side effects, which include pruritus, erythema, edema, and pain. (R)L-sulforaphane (SF) is a compound that protects against erythema, but it can also induce DNA fragmentation that leads to cell death by apoptosis. The aim of our study was to investigate whether SF has any impact on protoporphyrin IX (PpIX) production and on PDT effectiveness. We have investigated some relevant properties of SF: its photostability in dimethyl sulfoxide (DMSO), its effect on ALA-induced production of PpIX in A431 human squamous carcinoma cells and in human skin, its effect on the photoinactivation of PpIX sensitized cells, and its effect on the rate of photobleaching of PpIX. SF had no influence on PpIX photodegradation, neither in solution nor in A431 cells. The synthesis of PpIX was increased by SF in human skin, but not in A431 cells. The average increase in PpIX fluorescence in human skin was 18% +/- 6% and 43% +/- 10% for ALA combined with 80 nmol/L SF and 120 nmol/L SF, respectively. Pretreatment with (R)L-sulforaphane before topical ALA-PDT may improve penetration of ALA through the stratum corneum, and, subsequently, increase PpIX synthesis.