Parthenolide, a sesquiterpene lactone from the medical herb feverfew, shows anticancer activity against human melanoma cells in vitro

Abstract

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.

Chemical composition and biological activity of Tanacetum audibertii (Req.) DC. (Asteraceae), an endemic species of Sardinia Island, Italy

“…Many studies have been reported on the essential oil composition of various Tanacetum species (El-Shazly et al, 2002;Goren et al, 2001;Greche et al, 2000;Judzentiene and Mockute, 2005;Kandemir et al, 2008;MajedJabari et al, 2002;Marongiu et al, 2009;Mockute and Judzentiene, 2004;Monfared et al, 2002;Piras et al, 2014;Polatoglu et al, 2011;Rohloff et al, 2004;Weyerstahl et al, 1999) and camphor, 1,8-cineole, ␣-thujone, carvone, thymol, trans-sabinyl acetate, borneol, caryophyllene oxide, (E)-myroxide, sabinene, bornyl acetate, isopulegone and artemisia ketone were identified as the major constituents. This genus is also found to contain sesquiterpene lactones (Aljancic et al, 2001;Mahmood et al, 2002), a large group of molecules with several biological activities (Chaturvedi, 2011;Ghantous et al, 2010;Kreuger et al, 2012;Lesiak et al, 2010;Merfort, 2011;Wagner et al, 2008;Zhang et al, 2005).…”

Antimyeloma activity of the sesquiterpene lactone cnicin: impact on Pim-2 kinase as a novel therapeutic target

“…Sesquiterpene lactones are one class of natural compounds that display cytotoxic activities and different components purified from various sources have been found to efficiently kill cancer cells [5][6][7][8][9][10][11][12][13]. Depending on the source of the isolated compounds and the tumor entities tested, the related mechanisms of sesquiterpene lactone-induced apoptosis are multifaceted, including inhibition of NF-κB, accumulation of reactive oxygen species (ROS), cell cycle arrest, induction of endoplasmic reticulum stress, and activation of caspase 8.…”

Effect of parthenolide on growth and apoptosis regulatory genes of human cancer cell lines

“…(Asteraceae), commonly known as feverfew herb (Cretnik et al, 2005;Hamedi et al, 2013). Various biological activities, like antioxidant, anticancer, antimicrobial, and anti-inflammatory properties of T. parthenium, are attributed to the presence of parthenolide (Jain & Kulkarni, 1999;Kwok et al, 2001;Lesiak et al, 2010;Mohsenzadeh et al, 2011;Wu et al, 2006). Also, parthenolide has been reported for its anti-inflammatory, antileishmanial, antifungal, antioxidant, and anticancer properties (Hehner et al, 1999;Herrera et al, 2005;Mathema et al, 2012;Tiuman et al, 2005).…”