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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
St John's Wort (Hypericum perforatum L.) photomedicine: Hypericin-photodynamic therapy induces metastatic melanoma cell death
PLoS ONE, Volume 9, No. 7, Article e103762, Year 2014
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Description
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. © 2014 Kleemann et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC4116257/bin/pone.0103762.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC4116257/bin/pone.0103762.s002.tif
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https://efashare.b-cdn.net/share/pmc/articles/PMC4116257/bin/pone.0103762.s004.avi
https://efashare.b-cdn.net/share/pmc/articles/PMC4116257/bin/pone.0103762.s005.avi
Authors & Co-Authors
Kleemann, Britta
South Africa, Cape Town
University of Cape Town
Loos, Ben
South Africa, Stellenbosch
Stellenbosch University
Scriba, Thomas J.
South Africa, Cape Town
University of Cape Town
Lang, Dirk M.
South Africa, Cape Town
University of Cape Town
Davids, Lester Merlin
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 86
Authors: 5
Affiliations: 2
Identifiers
Doi:
10.1371/journal.pone.0103762
e-ISSN:
19326203
Research Areas
Cancer