A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer

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...

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Bibliographic Details
Published in:Oncotarget 2016-05, Vol.7 (22), p.31814-31824
Main Authors: He, Dong-Xu, Li, Guo-Hong, Gu, Xiao-Ting, Zhang, Liang, Mao, Ai-Qin, Wei, Juan, Liu, De-Quan, Shi, Gui-Yang, Ma, Xin
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Biotransformation
Breast Neoplasms - drug therapy
Breast Neoplasms - pathology
Cell Proliferation - drug effects
Delftia acidovorans - metabolism
Dose-Response Relationship, Drug
Drug Discovery - methods
Drug Resistance, Neoplasm - drug effects
Endophytes - metabolism
Epithelial-Mesenchymal Transition - drug effects
Female
Green Chemistry Technology
Humans
Liliaceae - microbiology
MCF-7 Cells
Mice, Nude
Research Paper
Saponins - metabolism
Saponins - pharmacology
Tumor Burden - drug effects
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.6674