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Anticancer Res. 2013 Aug;33(8):3205-12.

Parthenolide complements the cell death-inducing activity of doxorubicin in melanoma cells.

Author information

1
Department of Molecular Biology of Cancer, Medical University of Lodz, 6/8 Mazowiecka Street; 92-215 Lodz, Poland.

Abstract

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.

KEYWORDS:

ABCB5; NF-κB; doxorubicin; melanoma; p53; parthenolide

PMID:
23898080
[Indexed for MEDLINE]

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