Attenuation of Inflammatory Responses in Breast and Ovarian Cancer Cells by a Novel Chalcone Derivative and Its Increased Potency by Curcumin.

Abstract

Breast and ovarian cancers are two common malignancies in women and a leading cause of death globally. The aim of the present study was to explore the effects of a novel chalcone derivative 1-(4-(methylsulfonyl)phenyl)-3-(phenylthio)-3-(p-tolyl)propane-1-one (MPP) individually or combined with curcumin, a well-known herbal medicine with anticancer properties, as a new combination therapy on inflammatory pathways in breast and ovarian cancer cell lines. LPS-induced NF-κB DNA-binding activity and the levels of proinflammatory cytokines were measured in the MPP- and MPP-curcumin combination-treated MDA-MB-231 and SKOV3 cells by ELISA-based methods. The expression of COX2, INOS, and MMP9 genes and nitrite levels was also evaluated by real-time qRT-PCR and Griess method, respectively. IκB levels were evaluated by Western blotting. MPP significantly inhibited the DNA-binding activity of NF-κB in each cell line and subsequently suppressed the expression of downstream genes including COX2, MMP9, and INOS. The levels of proinflammatory cytokines, as well as NO, were also decreased in response to MPP. All the effects of MPP were enhanced by the addition of curcumin. MPP, especially when combined with curcumin, caused a remarkable increase in the concentration of IκB. MPP and its coadministration with curcumin effectively reduced the activity of the NF-κB signaling pathway, leading to a reduced inflammatory response in the environment of cancer cells. Thus, MPP, either alone or combined with curcumin, might be considered an effective remedy for the suppression of inflammatory processes in breast and ovarian cancer cells.