Evaluation of the antimetastatic and anticancer activities of morin in HER2‑overexpressing breast cancer SK‑BR‑3 cells

Lee,Kyu-Shik; Lee,Min-Gu; Nam,Kyung-Soo

doi:10.3892/or.2021.8077

Evaluation of the antimetastatic and anticancer activities of morin in HER2‑overexpressing breast cancer SK‑BR‑3 cells

Authors:
- Kyu-Shik Lee
- Min-Gu Lee
- Kyung-Soo Nam
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Affiliations: Department of Pharmacology and Intractable Disease Research Center, School of Medicine, Dongguk University, Gyeongju‑si, Gyeongsangbuk‑do 38066, Republic of Korea
Published online on: May 11, 2021 https://doi.org/10.3892/or.2021.8077
Article Number: 126

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Abstract

Morin (2',3,4',5,7‑pentahydroxyflavone), a flavonoid isolated from members of the Moraceae family and the leaves of Cudranaia tricuspidata Buread, is a well‑known natural substance with anti‑inflammatory, antioxidative, antimetastasis, and anticancer effects. However, its anticancer activity has not been comprehensively investigated in human epidermal growth factor receptor 2 (HER2)‑overexpressing breast cancer cells. Here, we evaluated the effects of morin on metastasis and cell viability in HER‑2‑overexpressing human breast cancer SK‑BR‑3 cells. Our results revealed that morin (150‑200 µM) prevented endothelial growth factor (EGF)‑induced metastatic potential and suppressed cell migration and MMP‑9 activity by inhibiting the EGFR signaling pathway in SK‑BR‑3 cells by gelatin zymography, wound healing assay and western blotting. Interestingly, morin‑induced reductions in cell viability were found to be associated with inhibition of the HER2/EGFR signaling pathway by sulforhodamine B assay and western blotting. Morin also induced the phosphorylation of H2A.X and downregulated the expression levels of RAD51 and survivin, which implied morin‑induced DNA damage and that this damage accumulated in HER‑2‑overexpressing SK‑BR‑3 cells. Western blot analysis and fluorescent immunocytochemisty showed that morin also activated autophagy after 24 h of treatment and this was maintained at 48 h when activation of apoptosis via PARP cleavage resulted in the activation of caspase‑3 and ‑7, which was associated with the release of cytochrome c to the cytosol from mitochondria. In addition, the phosphorylation of p38 and JNK was enhanced in the HER‑2‑overexpressing SK‑BR‑3 cells by morin after 24 and 48 h of treatment, which suggested p38 and JNK participate in morin‑induced cell death. Taken together, the present investigation indicates that morin is a powerful therapeutic candidate for the treatment of HER2‑overexpressing breast cancer because it suppresses the EGFR signaling pathway, induces cell death by inhibiting the HER2/EGFR signaling pathway, and suppresses metastatic potential.

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