St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death

dc.contributor.authorKleemann, Brittaen_ZA
dc.contributor.authorLoos, Benjaminen_ZA
dc.contributor.authorScriba, Thomas Jen_ZA
dc.contributor.authorLang, Dirken_ZA
dc.contributor.authorDavids, Lester Men_ZA
dc.date.accessioned2016-01-11T06:55:34Z
dc.date.available2016-01-11T06:55:34Z
dc.date.issued2014en_ZA
dc.description.abstractHypericin, an extract from St John's Wort ( Hypericum perforatum L. ), is a promising photosensitizer in the context of clinical photodynamic therapy due to its excellent photosensitizing properties and tumoritropic characteristics. Hypericin-PDT induced cytotoxicity elicits tumor cell death by various mechanisms including apoptosis, necrosis and autophagy-related cell death. However, limited reports on the efficacy of this photomedicine for the treatment of melanoma have been published. Melanoma is a highly aggressive tumor due to its metastasizing potential and resistance to conventional cancer therapies. The aim of this study was to investigate the response mechanisms of melanoma cells to hypericin-PDT in an in vitro tissue culture model. Hypericin was taken up by all melanoma cells and partially co-localized to the endoplasmic reticulum, mitochondria, lysosomes and melanosomes, but not the nucleus. Light activation of hypericin induced a rapid, extensive modification of the tubular mitochondrial network into a beaded appearance, loss of structural details of the endoplasmic reticulum and concomitant loss of hypericin co-localization. Surprisingly the opposite was found for lysosomal-related organelles, suggesting that the melanoma cells may be using these intracellular organelles for hypericin-PDT resistance. In line with this speculation we found an increase in cellular granularity, suggesting an increase in pigmentation levels in response to hypericin-PDT. Pigmentation in melanoma is related to a melanocyte-specific organelle, the melanosome, which has recently been implicated in drug trapping, chemotherapy and hypericin-PDT resistance. However, hypericin-PDT was effective in killing both unpigmented (A375 and 501mel) and pigmented (UCT Mel-1) melanoma cells by specific mechanisms involving the externalization of phosphatidylserines, cell shrinkage and loss of cell membrane integrity. In addition, this treatment resulted in extrinsic (A375) and intrinsic (UCT Mel-1) caspase-dependent apoptotic modes of cell death, as well as a caspase-independent apoptotic mode that did not involve apoptosis-inducing factor (501 mel). Further research is needed to shed more light on these mechanisms.en_ZA
dc.identifier.apacitationKleemann, B., Loos, B., Scriba, T. J., Lang, D., & Davids, L. M. (2014). St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death. <i>PLoS One</i>, http://hdl.handle.net/11427/16299en_ZA
dc.identifier.chicagocitationKleemann, Britta, Benjamin Loos, Thomas J Scriba, Dirk Lang, and Lester M Davids "St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death." <i>PLoS One</i> (2014) http://hdl.handle.net/11427/16299en_ZA
dc.identifier.citationKleemann, B., Loos, B., Scriba, T. J., Lang, D., & Davids, L. M. (2013). St John's Wort (Hypericum perforatum L.) Photomedicine: Hypericin-Photodynamic Therapy Induces Metastatic Melanoma Cell Death. PloS one, 9(7), e103762. doi:10.1371/journal.pone.0103762en_ZA
dc.identifier.ris TY - Journal Article AU - Kleemann, Britta AU - Loos, Benjamin AU - Scriba, Thomas J AU - Lang, Dirk AU - Davids, Lester M AB - Hypericin, an extract from St John's Wort ( Hypericum perforatum L. ), is a promising photosensitizer in the context of clinical photodynamic therapy due to its excellent photosensitizing properties and tumoritropic characteristics. Hypericin-PDT induced cytotoxicity elicits tumor cell death by various mechanisms including apoptosis, necrosis and autophagy-related cell death. However, limited reports on the efficacy of this photomedicine for the treatment of melanoma have been published. Melanoma is a highly aggressive tumor due to its metastasizing potential and resistance to conventional cancer therapies. The aim of this study was to investigate the response mechanisms of melanoma cells to hypericin-PDT in an in vitro tissue culture model. Hypericin was taken up by all melanoma cells and partially co-localized to the endoplasmic reticulum, mitochondria, lysosomes and melanosomes, but not the nucleus. Light activation of hypericin induced a rapid, extensive modification of the tubular mitochondrial network into a beaded appearance, loss of structural details of the endoplasmic reticulum and concomitant loss of hypericin co-localization. Surprisingly the opposite was found for lysosomal-related organelles, suggesting that the melanoma cells may be using these intracellular organelles for hypericin-PDT resistance. In line with this speculation we found an increase in cellular granularity, suggesting an increase in pigmentation levels in response to hypericin-PDT. Pigmentation in melanoma is related to a melanocyte-specific organelle, the melanosome, which has recently been implicated in drug trapping, chemotherapy and hypericin-PDT resistance. However, hypericin-PDT was effective in killing both unpigmented (A375 and 501mel) and pigmented (UCT Mel-1) melanoma cells by specific mechanisms involving the externalization of phosphatidylserines, cell shrinkage and loss of cell membrane integrity. In addition, this treatment resulted in extrinsic (A375) and intrinsic (UCT Mel-1) caspase-dependent apoptotic modes of cell death, as well as a caspase-independent apoptotic mode that did not involve apoptosis-inducing factor (501 mel). Further research is needed to shed more light on these mechanisms. DA - 2014 DB - OpenUCT DO - 10.1371/journal.pone.0103762 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death TI - St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death UR - http://hdl.handle.net/11427/16299 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16299
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0103762
dc.identifier.vancouvercitationKleemann B, Loos B, Scriba TJ, Lang D, Davids LM. St John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death. PLoS One. 2014; http://hdl.handle.net/11427/16299.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDepartment of Human Biologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2014 Kleemann et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherApoptosisen_ZA
dc.subject.otherMelanoma cellsen_ZA
dc.subject.otherCellular structures and organellesen_ZA
dc.subject.otherLysosomesen_ZA
dc.subject.otherCell membranesen_ZA
dc.subject.otherMitochondriaen_ZA
dc.subject.otherFluorescence microscopyen_ZA
dc.subject.otherMelanomasen_ZA
dc.titleSt John's Wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell deathen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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