Melanomas display increased cytoprotection to hypericin-mediated cytotoxicity through the induction of autophagy.
Photodynamic therapy (PDT) as a regime for melanoma is of limited success due to factors such as the efficacy of the photosensitizer used, penetration depth and the presence of pigment. We characterised a pigmented and an unpigmented melanoma cell line with respect to their phenotypes. Cell viability was assessed after exposure to hypericin, a UVA-activated photosensitizer. Exposure to 3 microM activated hypericin induced a cytoprotective (autophagic) response from both cell lines. However, the pigmented cells accumulated a large amount of glycogen in their cytoplasm. We hypothesise that the treatment induces an initial cytoprotective response through autophagy, but with increased stress results in a different mode of cell death in pigmented melanoma cells from unpigmented cells. These results indicate that hypericin-PDT could be an adjuvant therapy for melanoma.
Davids
Lester M
LM
Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Observatory, 7925 Cape Town, South Africa. lester.davids@uct.ac.za
Kleemann
Britta
B
Cooper
Susan
S
Kidson
Susan H
SH
D000873:Anthracenes; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008543:Melanins / Q000032:analysis; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010778:Photochemotherapy; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000648:ultrastructure; D014466:Ultraviolet Rays
D000873:Anthracenes; D008543:Melanins; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin; D014442:Monophenol Monooxygenase