Rosmanol induces breast cancer cells apoptosis by regulating PI3K/AKT and STAT3/JAK2 signaling pathways

迷迭香酚通过调控PI3K/AKT和STAT3/JAK2信号通路诱导乳腺癌细胞凋亡

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作者:Dongjun Jiang, Jiaqi Xu, Sitong Liu, Moussa Ide Nasser, Wei Wei, Tianjiao Mao, Xintong Liu, Xiaopan Zou, Jiang Li, Xiaomeng Li

Abstract

Breast cancer is one of the most frequently diagnosed cancers amongst women; however, there is currently no effective treatment. Natural compounds are considered to contribute to cancer prevention and have a pivotal role in modulating apoptosis. Rosmanol is a phenolic diterpene compound with antioxidant and anti-inflammatory properties. In the present study, the effects of Rosmanol on breast cancer cell proliferation/apoptosis were investigated, and it was demonstrated that it inhibited the proliferation of MCF-7 and MDA-MB 231 cells but did not have a significant effect on normal human breast MCF-10A cells. In addition, the apoptotic process was accelerated by Rosmanol, through mitochondrial pathways and reactive oxygen species (ROS) production caused by DNA damage, which function further demonstrated by the attenuation and addition of the ROS inhibitor, N-acetyl-cysteine. It was also demonstrated that Rosmanol accelerated cell apoptosis, and arrested breast cancer cells in the S phase. Moreover, Rosmanol inhibited proliferation and promoted apoptosis of cancer cells via the inhibition of ERK and STAT3 signals, attributable to the increase in p-p38, the overexpression of protein inhibitor of activated STAT3, and the decrease in PI3K/AKT, ERK and JAK2/STAT3.

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