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Anticancer Effects of a Korean Herbal Medicine Formula ( H 9) via AMPK and HER 2‐ PI 3 K / A kt Signaling in Breast Cancer Cells
Author(s) -
Lee JuHee,
Son Young Hoon,
Kwon YoungWon,
Park Sung Yun,
Koo ByungSoo,
Jung Seung Hyun
Publication year - 2017
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.5906
Subject(s) - ampk , trastuzumab , apoptosis , pi3k/akt/mtor pathway , medicine , protein kinase b , breast cancer , cell cycle , pharmacology , cancer , cancer research , chemistry , kinase , protein kinase a , biochemistry
An H9 is a formula of nine medicinal herbs derived from Osuyubujaijung ‐ tang , a traditional Korean prescription for Soeumin constitution. In our previous study, H9 showed anticancer effects against breast cancer and non‐small‐cell lung cancer. However, the underlying mechanisms of these effects have not yet been elucidated. In this study, we investigated the effects of H9, both alone and in combination with trastuzumab, on breast cancer cells and sought to elucidate the mechanisms involved. H9 suppressed the proliferation of human breast cancer cells, induced arrest of the cell cycle at the G0/G1 phase, and caused mitochondrial dysfunction and apoptosis. In addition, H9 induced the activation of AMPK and inhibited the HER2‐PI3K/Akt signaling pathway. Furthermore, H9 attenuated hypoxia‐induced HIF‐1α and VEGF, resulting in decreased migration and invasion of breast cancer cells. Compared with treatment with either drug alone, co‐treatment with H9 and trastuzumab significantly inhibited the growth of BT‐474 cells through induction of apoptosis. These results suggest that H9 should be considered as a potent anticancer agent that targets the HER2‐PI3K/Akt pathway, and the combination of H9 with trastuzumab should be considered as a new therapeutic regimen for treating breast cancer. Copyright © 2017 John Wiley & Sons, Ltd.