Dual down‐regulation of EGFR and ErbB2 by berberine contributes to suppression of migration and invasion of human ovarian cancer cells

Abstract

The overexpression of EGFR and/or ErbB2 occurs frequently in ovarian cancers and is associated with poor prognosis. The purpose of this study was to examine the anticancer effects and molecular mechanisms of berberine on human ovarian cancer cells with different levels of EGFR and/or ErbB2. We found that berberine reduced the motility and invasiveness of ovarian cancer cells. Berberine depleted both EGFR and ErbB2 in ovarian cancer cells. Furthermore, berberine suppressed the activation of the EGFR and ErbB2 downstream targets cyclin D1, MMPs, and VEGF by down‐regulating the EGFR‐ErbB2/PI3K/Akt signaling pathway. The berberine‐mediated inhibition of MMP‐2 and MMP‐9 activity could be rescued by co‐treatment with EGF. Finally, we demonstrated that berberine induced ErbB2 depletion through ubiquitin‐mediated proteasome degradation. In conclusion, the suppressive effects of berberine on the ovarian cancer cells that differ in the expression of EGFR and ErbB2 may be mediated by the dual depletion of EGFR and/or ErbB2.

Anticancer Effects and Mechanisms of Berberine from Medicinal Herbs: An Update Review

“…Moreover, the EGFR or ERBB2 overexpression could cause resistance to ovarian cancer cell death and increase tumor-initiating capacity [ 99 ]. The evidence suggested that berberine consumed EGFR and ERBB2 in ovarian cancer cells and inhibited the activation of EGFR and ERBB2 downstream targets cyclin D1, MMPs, and VEGF via the EGFR-ERBB2/PI3K/Akt signaling pathway [ 100 ].…”

Gut Microbiota and Metabolome Alterations Associated with Chinese Monks’ Practice

“…Therefore, we believe that the long-term meditation of monks promotes the brain to think, protects the function of the brain, and prevents neurodegenerative diseases. Many studies have reported that solasodine [47], peimine [48], berberine [49], ginkgoic acid [50], and 6-pentadecyl salicylic acid [51] have antimetastatic effects and inhibit tumor cell proliferation in various cancers. Therefore, the practices of meditation and vegetarianism may help monks prevent cancer.…”

Anticancer Potential of Natural Isoquinoline Alkaloid Berberine

“…Berberine reduced the expression of EGFR, ErbB2, cyclin D1, MMP-2/9, and VEGF in all cell lines except ErbB2 in MDAH-2774 cells (Table 1). 131 SKOV3 and 3AO cells exposed to 2.5, 5, 10, 20, 40, 80, 160, and 320 µM berberine had decreased levels of cell proliferation depending on the concentration, with IC 50 values of 78.52 µM and 125.8 µM, respectively. Berberine attenuated cell migration and invasion by promoting miR-145 expression and reducing MMP16, a target of miR-145 (Table 1).…”