A new agent developed by biotransformation of polyphyllin VII inhibits chemoresistance in breast cancer
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Dong-Xu He1,*, Guo-Hong Li2,*, Xiao-Ting Gu1,*, Liang Zhang1, Ai-Qin Mao1, Juan Wei1, De-Quan Liu3, Gui-Yang Shi1, Xin Ma1
1School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China
2Laboratory for Conservation and Utilization of Bio-Resources, and Key Laboratory for Microbial Resources of The Ministry of Education, Yunnan University, Kunming 650091, China
3Department of Breast Surgery, The Third Affiliated Hospital, Kunming Medical University, Kunming 650031, China
*These authors have contributed equally to this work
Xin Ma, email: [email protected]
Gui-Yang Shi, email: [email protected]
De-Quan Liu, email: [email protected]
Keywords: biotransformation; endophyte; polyphyllin VII; cancer; chemoresistance
Received: August 06, 2015 Accepted: December 05, 2015 Published: December 19, 2015
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.
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