Cellular Mechanisms and Prospective Applications of Hypericin in Photodynamic Therapy

Abstract

During the last decades, Photodynamic Therapy (PDT) has been established as a powerful alternative approved by health agencies of several countries for treatment of various malignant and some non-malignant diseases. PDT makes use of the light-induced destruction of target cells by formation of cytotoxic products in the presence of a photosensitizing agent and oxygen. The light-dependent tumor destructive properties of Hypericin have drawn attention to its promising application as a photosensitizer in the frame of PDT. Hypericin is a naturally occurring secondary metabolite in plants of the Hypericum genus, with Hypericum perforatum (St. John's wort) as it is a commonly known representative. This review focuses on the cellular mechanisms of Hypericin-based phototoxicity and provides an outlook for future application of Hypericin as a fluorescing and photosensitizing agent for diagnosis and treatment of cancerous diseases, respectively.

Time-resolved gene expression profiling of human squamous cell carcinoma cells during the apoptosis process induced by photodynamic treatment with hypericin

“…Hypericin localizes predominantly in intracellular membranes such as ER, Golgi apparatus ( Fig. 1) and, under different treatment conditions, in the mitochondrial and nuclear membrane as well as in lysosomes (91). Accordingly ER stress response is an early event following hypericin-PDT leading to apoptosis, which can be executed via caspase-dependent or -independent pathways (92).…”

Melanoma resistance to photodynamic therapy: new insights

“…Due to melanoma's intrinsic resistance to radiation and chemotherapeutic drugs, PDT has been suggested as an alternative therapeutic modality, which involved light induced destruction of cells or target tissues through sensitization to light by various photosensitizing agents; hypericin (Hadjur, Richard et al 1996), benzoporphyrin derivatives (Busetti, Soncin et al 1999) or protophorphyrin IX (PPIX) being just a few examples (Kiesslich, Krammer et al 2006). However, several resistance mechanisms such as; optical interference (Hadjur, Richard et al 1996;Busetti, Soncin et al 1999), anti-oxidant defense mechanisms of melanin (Hadjur, Richard et al 1996;Davids, Kleemann et al 2009), cytoprotective response through induction of autophagy (Davids, Kleemann et al 2009), melanosomes protecting melanocytes and melanoma cells against harmful effects of toxic intermediates (Davids, Kleemann et al 2009) and lastly ABCG2 transporters acting as efflux pumps making cells capable of eliminating toxic amounts of porphyrins (Bebes, Nagy et al 2011) cause reduction in efficacy of PDT on melanoma cells.…”

Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol

“…Under light illumination Hyp displays antiproliferative and cytotoxic effects on many tumor cell lines. This property, together with minimal dark toxicity, certain tumor selectivity and high clearance rate from the host body, enables this compound to belong between the most effective natural photosensitizers (see reviews Miskovsky 2002;Kiesslich et al 2006;Kober et al 2008;Kramer and Verwanger 2012).…”