title: A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer.
abstract: Biotransformation by the endophytes of certain plants changes various compounds, and this 'green' chemistry becomes increasingly important for finding new products with pharmacological activity. In this study, polyphyllin VII (PPL7) was biotransformed by endophytes from the medicinal plant Paris polyphylla Smith, var. yunnanensis. This produced a new compound, ZH-2, with pharmacological activity in vitro and in vivo. ZH-2 was more potent than PPL7 in selectively killing more chemoresistant than chemosensitive breast cancer cells. ZH-2 also re-sensitized chemoresistant breast cancer cells, as evidenced by the improved anti-cancer activity of commonly-used chemotherapeutic agent in vitro, in vivo, and in clinical samples. This anti-chemoresistance effect of ZH-2 was associated with inhibiting the epithelial-mesenchymal transition (EMT) pathway. Taken together, our findings are the first one to link biotransformation with a biomedicine. The results provide insights into developing new pharmacologically-active agents via biotransformation by endophytes.
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: He
authors.affiliation: Laboratory for Conservation and Utilization of Bio-Resources, and Key Laboratory for Microbial Resources of The Ministry of Education, Yunnan University, Kunming 650091, China.
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xiao-Ting
authors.initials: XT
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Mao
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University, Kunming 650031, China.
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Gui-Yang
authors.initials: GY
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001711:Biotransformation; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D020605:Delftia acidovorans / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000379:methods*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D060026:Endophytes / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D055772:Green Chemistry Technology; D006801:Humans; D019668:Liliaceae / Q000382:microbiology; D061986:MCF-7 Cells; D008819:Mice, Nude; D012503:Saponins / Q000378:metabolism* / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D012503:Saponins; C000625668:ZH-2 compound; C585643:polyphyllin VII
keywords: biotransformation; cancer; chemoresistance; endophyte; polyphyllin VII