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F3, a novel active fraction of Valeriana jatamansi Jones induces cell death via DNA damage in human breast cancer cells

Zhu, Zhihui, Shen, Weifeng, Tian, Shasha, Yang, Bo, Zhao, Huajun
Phytomedicine 2019 v.57 pp. 245-254
DNA damage, Valeriana jatamansi, Western blotting, antineoplastic activity, apoptosis, autophagy, breast neoplasms, cell viability, epithelium, flow cytometry, fluorescence microscopy, fluorescent antibody technique, human cell lines, humans, in vivo studies, membrane potential, mice, mitochondrial membrane, mitogen-activated protein kinase, models, neoplasm cells, proteins, staining, toxicity testing, traditional medicine
F3 is a novel fraction, for the first time isolated from Valeriana jatamansi Jones, which is a traditional Chinese folk medicine. Its anti-cancer potential and the underlying molecular mechanisms have not been well elucidated.This study aims to investigate the anti-cancer effects of F3 on human breast cancer cell lines and its underlying mechanisms.MTT assay was first performed to detect the effect of F3 on cell viability in human breast cancer cell lines and human mammary epithelial MCF-10A cells. Cell apoptosis, mitochondrial membrane potential and ROS level were detected by flow cytometry. Comet and immunofluorescence assays were utilized to assess DNA damage and expression of γ-H2AX. Autophagy were observed by AO staining and fluorescence microscopy. The expression of relative proteins was detected by western blotting. The xenograft model in nude mice was used to elucidate the effect of F3 on tumor growth and DNA damage in vivo.F3 could significantly inhibit the growth of breast cancer cells in concentration-dependent manner by inducing apoptosis and has no obvious inhibitory effect of the growth on MCF-10A cells. Mechanistic studies demonstrated that F3-induced apoptosis was mediated by DNA damage as presented by DNA strand breaks and γ-H2AX activation that might be attacked by ROS accumulation. This triggered several key molecular events involving activation of MAPKs pathway. Further study showed that F3 induced autophagy with the autophagosome formation and increased LC3-II levels. Finally, in vivo study, F3 exhibited a potential antitumor effect and induced DNA damage in MDA-MB-231 xenografts.The antitumorigenic activity of F3 was found in vitro and in vivo. These data suggest that F3 may be a potential natural active fraction for the treatment of human breast cancer.