Phloroglucinol suppresses metastatic ability of breast cancer cells by inhibition of epithelial‐mesenchymal cell transition

Abstract

Metastasis is a challenging clinical problem and the primary cause of death in breast cancer patients. However, there is no therapeutic agent against metastasis of breast cancer cells. Here we report that phloroglucinol, a natural phlorotannin component of brown algae suppresses metastatic ability of breast cancer cells. Treatment with phloroglucinol effectively inhibited mesenchymal phenotypes of basal type breast cancer cells through downregulation of SLUG without causing a cytotoxic effect. Importantly, phloroglucinol decreased SLUG through inhibition of PI3K/AKT and RAS/RAF-1/ERK signaling. In agreement with in vitro data, phloroglucinol was also effective against in vivo metastasis of breast cancer cells, drastically suppressing their metastatic ability to lungs, and extending the survival time of mice. Collectively, our findings demonstrate a novel anticancer activity of phloroglucinol against metastasis of breast cancer cells, implicating its clinical relevance.

The prognostic implication of slug in all tumour patients – a systematic meta‐analysis

“…Some Slug inhibitors have been proved to be effective. Phloroglucinol can suppress basal-type breast cancer cells by downregulating Slug both in vitro and in mouse [3]. Significant reduction of Slug expression was also observed in patients with breast cancer after neoadjuvant chemotherapy [51].…”

Bioactive compounds from brown seaweeds: Phloroglucinol, fucoxanthin and fucoidan as promising therapeutic agents against breast cancer

“…In the same study phloroglucinol also decreased primary tumor formation and inhibit EMT in vivo. A reduction of breast cancer infiltration in 3D-culture system was also reported (Kim et al, 2015).…”

“…The eventual toxicity of phloroglucinol in normal cells has not been reported yet. Rather, it has been shown cytoprotective effects on oxidative stress induced cell damage in several models (Kang et al, 2006;Kang et al, 2010;Kim et al, 2015). Beside the extensively interest in medicine, phloroglucinol has been used also in cosmetics, textiles, pesticides, paints and cements (Kim et al, 2015;Singh et al, 2010).…”

Seaweed Secondary Metabolites with Beneficial Health Effects: An Overview of Successes in In Vivo Studies and Clinical Trials

“…NOD scid gamma mice 25 mg/kg (b.w.) 33.3% less metastasis of breast cancer cells and extended survival rate (40% after 10 weeks against 0% untreated group) [36].…”

“…Phloroglucinol 1 also exhibits breast anticancer activity at 25 mg/kg (b.w. ), either by decreasing tumor growth or by suppressing the metastatic ability of breast cancer cells that spread to the lungs, contributing in both cases to an increase of survival time in mice (Table 1) [35,36]. Since there is still no suitable therapeutic agent that blocks the progression of breast cancer, these results can be of clinical importance for the treatment of metastatic breast cancer.…”