The Multifaceted Photocytotoxic Profile of Hypericin

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Abstract

Photodynamic therapy (PDT) is an established anticancer treatment employing a phototoxin (photosensitizer), visible light and oxygen. The latter is photochemically converted into reactive oxygen species, which are highly toxic to the cells. Hypericin, a natural pigment of hypericum plants, is prominent among photosensitizers. The unique perylenequinone structure of hypericin is responsible for its intriguing multifaceted photochemical cytotoxicity. The diverse photodynamic action of hypericin targets a range of subcellular organelles most importantly the mitochondria and the endoplasmic reticulum (ER)-Golgi complex. Hypericin exerts its phototoxicity through intricate mechanisms, implicating key proteins, vital enzymes, organelle membranes and changes in cellular homeostasis. This, depending on drug and light administration conditions, leads to cell death, which occurs mainly by the induction of apoptosis and/or necrosis. Cell photosensitization with hypericin is also associated with the stimulation of macroautophagy, which may promote cell demise when the apoptotic machinery is defective. Herein, we aim to integrate the most important findings with regard to hypericin photocytotoxicity, into a unified scenario, detailing its potential in cancer photomedicine.

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