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Phytomedicine. 2018 Nov 15;50:43-49. doi: 10.1016/j.phymed.2018.08.004. Epub 2018 Aug 7.

Berberine down-regulates IL-8 expression through inhibition of the EGFR/MEK/ERK pathway in triple-negative breast cancer cells.

Author information

1
Department of Breast Cancer Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea. Electronic address: sangmin3005.kim@samsung.com.
2
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea.
3
Department of Breast Cancer Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea; Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea.
4
Department of Breast Cancer Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea; Department of Surgery, Samsung Medical Center, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 50 Irwon-dong, Gangnam-gu, Seoul 06351, South Korea. Electronic address: paojlus@hanmail.net.

Abstract

BACKGROUND:

Interleukin-8 (IL-8) expression is associated with metastasis in a variety of cancer cells.

PURPOSE:

Here, we investigated the regulatory mechanism of IL-8 expression as well as the pharmacological effect of berberine (BBR) on IL-8 expression in triple-negative breast cancer (TNBC) cells.

METHODS:

The clinical value of IL-8 was analyzed by from a public database [Kaplan‑Meier plotter database. IL-8 mRNA and protein expression was analyzed by real-time PCR and ELISA, respectively. Cell invasion was analyzed by Boyden chamber assay. Tumor cell growth was analyzed by colony forming assay.

RESULTS:

Clinically, we observed that breast cancer patients with highly expressed IL-8 are associated with poor outcomes in areas such as relapse-free, overall, and distant metastasis-free survival. We showed that IL-8 expression is higher in TNBC cells than in non-TNBC cells. In addition, the rates of cell invasion were significantly increased by IL-8 treatment. These IL-8 levels were decreased by EGFR (Neratinib and Afatinib) and MEK (PD98059) inhibitors in TNBC cells. Finally, we observed that BBR dramatically suppresses IL-8 expression. In addition, BBR also inhibited cell invasiveness and anchorage-independent growth. Interestingly, our results showed that BBR down-regulates EGFR protein expression and dose-dependently inhibits MEK and ERK phosphorylation.

CONCLUSION:

Here, we demonstrate that BBR may be a promising drug to suppress cell invasiveness and growth of TNBC through IL-8-related mechanisms.

KEYWORDS:

Berberine; Cell invasion; IL-8; MEK/ERK pathway; Triple-negative breast cancer

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