Gold-conjugated resveratrol nanoparticles attenuate the invasion and MMP-9 and COX-2 expression in breast cancer cells

Park,Sun Young; Chae,Seon Yeong; Park,Jin Oh; Lee,Kyu Jin; Park,Geuntae

doi:10.3892/or.2016.4716

Gold-conjugated resveratrol nanoparticles attenuate the invasion and MMP-9 and COX-2 expression in breast cancer cells

Authors:
- Sun Young Park
- Seon Yeong Chae
- Jin Oh Park
- Kyu Jin Lee
- Geuntae Park
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Affiliations: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan 609-735, Republic of Korea, Department of Nano Fusion Technology, Graduate School, Pusan National University, Busan 609-735, Republic of Korea
Published online on: March 29, 2016 https://doi.org/10.3892/or.2016.4716
Pages: 3248-3256

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Abstract

Gold nanoparticles (AuNPs) with antitumorigenic effects obstruct the initiation, development and progression of tumors via the regulation of various processes, such as proliferation and apoptosis. However, the effects of AuNPs on breast cancer metastasis have not been well studied, and their response to 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulation remains unclear. Therefore, we synthesized resveratrol-capped gold nanoparticles (Rev-AuNPs) using green nanotechnology and investigated their potential anti-invasive properties in human breast cancer cells in response to TPA stimulation. The Rev-AuNPs formed spherical nanoparticles of 22.28±2.98 nm in diameter. Next, we found that non-cytotoxic concentrations of Rev-AuNPs significantly suppressed the TPA-induced migration and invasion abilities of breast cancer cells. Rev-AuNPs suppressed TPA-induced enzymatic activity and the expression of matrix metalloproteinase (MMP)-9 and cyclooxygenase-2 (COX-2). Furthermore, Rev-AuNP treatment remarkably downregulated TPA-induced nuclear translocation and transcriptional activation of nuclear transcription factor-κB (NF-κB) and activator protein-1 (AP-1). Rev-AuNPs reduced the phosphorylation of phosphoinositide 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase (ERK)1/2 signaling, but did not affect the phosphorylation of Jun N-terminal kinase (JNK) or p38 MAPK in the TPA-stimulated breast cancer cells. Notably, Rev-AuNPs generally showed better anti-invasive activity than resveratrol without cytotoxicity. The inhibitory effect of Rev-AuNPs on MMP-9, COX-2, NF-κB, AP-1, PI3K/Akt and ERK activation was stronger than that of resveratrol for the same concentrations. We also demonstrated that Rev-AuNPs induced heme oxygenase-1 (HO-1) expression and that the inhibition of MMP-9 and COX-2 expression and MMP-9 enzymatic activity of Rev-AuNPs were abrogated by siRNA knockdown of HO-1 expression. Our findings revealed that the anti-invasive effects of Rev-AuNPs in response to TPA-stimulation were mediated by the suppression of MMP-9, COX-2, NF-κB, AP-1, PI3K/Akt and ERK and/or the activation of HO-1 signaling cascades. This novel finding emphasizes the pharmacological ability of Rev-AuNPs to treat breast cancer metastasis.

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