TY - JOUR T1 - Parthenolide Complements the Cell Death-inducing Activity of Doxorubicin in Melanoma Cells JF - Anticancer Research JO - Anticancer Res SP - 3205 LP - 3212 VL - 33 IS - 8 AU - MICHAL WOZNIAK AU - AGATA SZULAWSKA-MROCZEK AU - MARIUSZ L. HARTMAN AU - DARIUSZ NEJC AU - MALGORZATA CZYZ Y1 - 2013/08/01 UR - http://ar.iiarjournals.org/content/33/8/3205.abstract N2 - 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. ER -