Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro.
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.
Lesiak
Karolina
K
Department of Molecular Biology of Cancer, Medical University of Lodz, Lodz, Poland.
Koprowska
Kamila
K
Zalesna
Izabela
I
Nejc
Dariusz
D
Düchler
Markus
M
Czyz
Malgorzata
M
D000111:Acetylcysteine / Q000494:pharmacology; D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004347:Drug Interactions; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008875:Middle Aged; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D020903:Tanacetum parthenium / Q000737:chemistry*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C002669:parthenolide; D053148:Caspase 3; D000111:Acetylcysteine