RT Journal Article SR Electronic T1 Parthenolide Complements the Cell Death-inducing Activity of Doxorubicin in Melanoma Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3205 OP 3212 VO 33 IS 8 A1 MICHAL WOZNIAK A1 AGATA SZULAWSKA-MROCZEK A1 MARIUSZ L. HARTMAN A1 DARIUSZ NEJC A1 MALGORZATA CZYZ YR 2013 UL http://ar.iiarjournals.org/content/33/8/3205.abstract AB Background: Melanoma is characterized by high resistance to chemotherapy. The aim of this study was to investigate combined effects of doxorubicin and parthenolide on melanoma cells. Materials and Methods: Thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry were used to evaluate viability. The p53 levels and Poly-ADP ribose polymerase (PARP) cleavage were assessed by western blot. Electrophoretic mobility shift assay (EMSA) and quantitative real-time polymerase chain reaction (qRT-PCR) were used to evaluate changes in nuclear factor-κB (NF-κB) activity and gene expression, respectively. Results: Both drugs reduced the viability of melanoma cells and induced apoptosis. Expression of the ATP-binding cassette sub-family B member-5 (ABCB5) transporter was enhanced by doxorubicin. Doxorubicin induced activity of p53 and NF-κB. Parthenolide markedly reduced the constitutive and doxorubicin-induced NF-κB activity measured as the nuclear NF-κB, and expression of matrix metalloproteinase-9 (MMP9) and it had no effect on p53. Discussion: Doxorubicin and parthenolide affected distinct pathways in melanoma, and parthenolide was capable of combating some pro-survival effects of doxorubicin in the combined treatment. This provides a rationale for in vivo investigation of this drug combination.