Metastatic
melanoma is a highly life-threatening disease. The lack of response to
radiotherapy and
chemotherapy highlights the critical need for novel treatments.
Parthenolide, an active component of feverfew (Tanacetum parthenium), inhibits proliferation and kills various
cancer cells mainly by inducing apoptosis. The aim of the study was to examine anticancer effects of
parthenolide in
melanoma cells in vitro. The cytotoxicity of
parthenolide was tested in
melanoma cell lines and melanocytes, as well as
melanoma cells directly derived from a surgical excision. Adherent cell proliferation was measured by tetrazolium derivative reduction assay. Loss of the plasma membrane integrity, hypodiploid events,
reactive oxygen species generation, mitochondrial membrane potential dissipation, and
caspase-3 activity were assessed by flow cytometric analysis. Microscopy was used to observe morphological changes and cell detachment.
Parthenolide reduced the number of viable adherent cells in
melanoma cultures. Half maximal inhibitory concentration values around 4 mumol/l were determined. Cell death accompanied by mitochondrial membrane depolarization and
caspase-3 activation was observed as the result of
parthenolide application. Interestingly, the
melanoma cells from vertical growth phase and melanocytes were less susceptible to
parthenolide-induced cell death than metastatic cells when
drug concentration was at least 6 mumol/l.
Reactive oxygen species level was not significantly increased in
melanoma cells. However, preincubation of
parthenolide with the
thiol nucleophile N-acetyl-
cysteine protected
melanoma cells from
parthenolide-induced cell death suggesting the reaction with intracellular
thiols as the mechanism responsible for
parthenolide activity. In conclusion, the observed anticancer activity makes
parthenolide an attractive
drug candidate for further testing in
melanoma therapy.