title: Jatamanvaltrate P induces cell cycle arrest, apoptosis and autophagy in human breast cancer cells in vitro and in vivo.
abstract: Jatamanvaltrate P is a novel iridoid ester isolated from Valeriana jatamansi Jones, a traditional medicine used to treat nervous disorders. In this study, we found that Jatamanvaltrate P possessed notable antitumor properties and therefore evaluated its anticancer effects against human breast cancer cells in vitro and in vivo. Jatamanvaltrate P inhibited the growth and proliferation of MCF-7 and triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, MDA-MB-453 and MDA-MB-468) in a concentration-dependent manner, while displayed relatively low cytotoxicity to human breast epithelial cells (MCF-10A). Treatment with Jatamanvaltrate P induced G2/M-phase arrest in TNBC and G0/G1-phase arrest in MCF-7 cells. Further study of the molecular mechanisms of this cytotoxic compound demonstrated that Jatamanvaltrate P enhanced cleavage of PARP and caspases, while decreased the expression levels of cell cycle-related Cyclin B1, Cyclin D1 and Cdc-2. It also activated autophagy, as indicated by the triggered autophagosome formation and increased LC3-II levels. Autophagy inhibition by 3-MA co-treatment undermined Jatamanvaltrate P-induced cell death. Finally, Jatamanvaltrate P exhibited a potential antitumor effect in MDA-MB-231 xenografts without apparent toxicity. These results suggest that Jatamanvaltrate P is a potential therapeutic agent for breast cancer, providing a basis for development of the compound as a novel chemotherapeutic agent.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Tian
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lsy@zcmu.edu.cn.
authors.forename: Siyue
authors.initials: S
authors.lastname: Lou
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: zhj@zcmu.edu.cn.
authors.forename: Huajun
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology*; D014632:Valerian / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D039823:Iridoids; C000600596:jatamanvaltrate P
keywords: Apoptosis; Autophagy; Breast cancer; Cell cycle; Jamanvaltrate P