Structure Elucidation and Anti-Tumor Activities of Trichothecenes from Endophytic Fungus Fusariumsporotrichioides

Biomolecules

Si-Yang Dai¹  Ya-Jing Wang¹  Xue Song¹  Yong-Fu Lu¹  Nan Ma¹  Chang Li¹  Yue-Hu Pei¹  Yi Sun² 

[1] Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin 150081, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China;

关键词: trichothecene;    apoptosis;    cell cycle arrest;    mitochondrial pathway;    anti-tumor;   

DOI  :  10.3390/biom12060778

来源: DOAJ

【 摘 要 】

The secondary metabolites of Fusarium sporotrichioides, an endophytic fungus with anti-tumor activity isolated from Rauvolfia yunnanensis Tsiang, were investigated. Five trichothecenes, including one previously undescribed metabolite, were isolated and identified. Their structures were elucidated by means of extensive spectroscopic methods; the absolute configuration of compound 1 was determined by the ECD method. Surprisingly, 8-n-butyrylneosolaniol (3) exhibited stronger anti-tumor activity than T-2 toxin against Huh-7 cell line, with an IC₅₀ value of 265.9 nM. 8-n-butyrylneosolaniol (3) promoted apoptosis induction in Huh-7 cells. Moreover, cell cycle analysis showed that cell cycle arrest caused by 8-n-butyrylneosolaniol (3) at the G2/M phase resulted in cell proliferation inhibition and pro-apoptotic activity. Further studies showed a significant decrease in mitochondrial membrane permeabilization and a significant increase in ROS generation, which led to the activation of caspase cascades and subsequent cleavage of PARP fragments. In conclusion, 8-n-butyrylneosolaniol (3) induced cell apoptosis in Huh-7 cells via the mitochondria-mediated apoptotic signaling pathway, which could be a leading compound for anti-tumor agents.

【 授权许可】

Unknown