Sanguinarine inhibits invasiveness and the MMP‑9 and COX‑2 expression in TPA-induced breast cancer cells by inducing HO-1 expression

Park,Sun  Young; Jin,Mei  Ling; Kim,Young  Hun; Lee,Sang-Joon; Park,Geuntae

doi:10.3892/or.2013.2843

Sanguinarine inhibits invasiveness and the MMP‑9 and COX‑2 expression in TPA-induced breast cancer cells by inducing HO-1 expression

Authors:
- Sun Young Park
- Mei Ling Jin
- Young Hun Kim
- Sang-Joon 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 Microbiology, Pusan National University, Busan 609-735, Republic of Korea, Institute for Research and Industry Cooperation, Pusan National University, Busan 609-735, Republic of Korea
Published online on: November 12, 2013 https://doi.org/10.3892/or.2013.2843
Pages: 497-504

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Abstract

Most complications of breast cancer are attributed to metastasis to distant organs, including lymph nodes, bone, lung and liver. Metastasis is considered the leading cause of mortality in patients with breast cancer. The emergence of anti-metastatic properties in breast cancer is an important clinical phenomenon affecting long-term survival. In the present study, we investigated the anti-invasive mechanism of sanguinarine by focusing on its role in inducing HO-1 in breast cancer cells. The results showed that sanguinarine inhibited TPA-induced MMP-9 and COX‑2 mRNA and protein expression in a dose-dependent manner at non-cytotoxic concentrations. Similarly, the MMP-9 enzymatic activity and the PGE2 levels significantly decreased in MCF-7 breast cancer cells. TIMP‑1 and TIMP-2, specific endogenous inhibitors of MMP-9, were slightly induced by sanguinarine. Subsequent studies revealed that sanguinarine suppressed TPA-induced NF-κB and AP-1 activation, as well as the phosphorylation of Akt and ERK. Furthermore, sanguinarine significantly inhibited TPA-induced invasion and migration in breast cancer cells. We also demonstrated that sanguinarine induced HO-1 expression, and that the inhibition of MMP-9 and COX-2 expression and the enzymatic activity of sanguinarine were abrogated by siRNA-mediated knockdown of HO-1 expression. Thus, knockdown of endogenous HO-1 decreased TPA-induced cell invasion. Overall, the results of the present study demonstrate that HO-1 plays a pivotal role in the anti-invasive response of sanguinarine in TPA-stimulated breast cancer cells.

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