Molecular aspects of photodynamic therapy : low energy pre-sensitization of hypericin-loaded human endometrial carcinoma cells enhances photo-tolerance , alters gene expression and a ¡ ects the cell cycle

Photodynamic therapy (PDT) is a relatively young cancer treatment based on the application (topic or systemic) of a photosensitizing agent that accumulates in target tissues [1,2]. Upon irradiation with tissue-penetrating light, the activated photosensitizer produces reactive oxygen species that lead to cell death. The mechanisms that control cell death vary according to cell type and the type of photosensitizer [3]. Advances in PDT will probably depend on the discovery of new chromophores and the characterization of those already being used. The natural non-toxic chromatophore hypericin [4] is attracting renewed attention because of its potential as a photosensitizing anti-cancer drug. Indeed, neoplastic cells in culture respond to hypericin in a dose-dependent fashion: high doses of light and high concentrations of photosensitizer cause apoptosis or cell necrosis [5], whereas low levels of activation induce only a `stress response [6] that involves the synthesis of proteins known as stress-induced or heat shock proteins (HSP) [7]. The main function of HSP is to a¡ord additional protection to the cell as the need arises. Induction of HSP appears to coincide with acquisition of tolerance to high levels of stress that would otherwise kill the cell [8,9]. Because PDT induces cell damage via oxidative stress, we investigated, in HEC1-B cells, whether sub-lethal photosensitization confers resistance against further photo-induced damage, reduces apoptosis and preserves cell proliferation.