He Dong-Xu, Li Guo-Hong, Gu Xiao-Ting, Zhang Liang, Mao Ai-Qin, Wei Juan, Liu De-Quan, Shi Gui-Yang, Ma Xin
School of Pharmaceutical Sciences National Engineering, and Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China.
Laboratory for Conservation and Utilization of Bio-Resources, and Key Laboratory for Microbial Resources of The Ministry of Education, Yunnan University, Kunming 650091, China.
Oncotarget. 2016 May 31;7(22):31814-24. doi: 10.18632/oncotarget.6674.
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.
某些植物内生菌的生物转化会改变各种化合物，这种“绿色”化学对于寻找具有药理活性的新产品变得越来越重要。在本研究中，重楼皂苷VII（PPL7）被药用植物滇重楼的内生菌进行了生物转化。这产生了一种新的化合物ZH-2，其在体外和体内均具有药理活性。ZH-2在选择性杀死化疗耐药的乳腺癌细胞方面比PPL7更有效，且化疗耐药的乳腺癌细胞比化疗敏感的乳腺癌细胞更多。ZH-2还使化疗耐药的乳腺癌细胞重新敏感，体外、体内及临床样本中常用化疗药物抗癌活性的提高证明了这一点。ZH-2的这种抗化疗耐药作用与抑制上皮-间质转化（EMT）途径有关。综上所述，我们的发现首次将生物转化与生物医学联系起来。这些结果为通过内生菌生物转化开发新的药理活性剂提供了思路。
