构树内生真菌P-L12和C-J1代谢产物的抗肿瘤活性研究  

Antitumor activity of secondary metabolites from endophytic fungi P-L12 and C-J1 from Broussonetia papyrifera

作　　者：郑佳东 王红霞 许重远[3] 黄宝康[1,2] ZHENG Jia-dong;WANG Hong-xia;XU Zhong-yuan;HUANG Bao-kang(School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian Province,China;Schoolof Pharmacy,Naval Medical University,Shanghai 200433,China;Clinical Pharmacy Center,Nanfang Hospital,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]海军军医大学药学院,上海200433 [3]南方医科大学南方医院临床药学中心,广东广州510515

出　　处：《中国临床药理学杂志》2023年第10期1427-1430,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81773831)。

摘　　要：目的探究从矿区构树组织分离的2株内生真菌葡萄座腔菌(Botryos-phaeriadothidea,P-L12)和燕麦镰刀菌(Fusarium avenaceum,C-J1)的抗肿瘤活性并分析其代谢产物的化学成分。方法体外培养指数增长期的5种肿瘤细胞,以噻唑蓝(MTT)法测定2株内生真菌次生代谢产物的抗肿瘤活性。在药物处理48h后,测定不同条件下细胞的增殖情况,计算受试2种次生代谢产物的半抑制浓度(IC50)并进行趋势分析。用液相色谱-质谱联用(LC-MS)法分析2株内生真菌代谢产物的化学成分,明确其物质基础。结果2株内生真菌发酵产物乙酸乙酯部位提取物对5种肿瘤细胞均具有抑制作用。作用48h后C-J1有较强的细胞毒性作用,对人肝癌细胞HepG2的抑制作用最强,IC50为(14.21±1.56)μg·mL^(-1),对其余4种肿瘤细胞也有较强的细胞毒活性。P-L12的次生代谢产物仅对人前列腺癌细胞DU-145具有较强的抑制作用,其IC50为(9.96±3.00)μg·mL^(-1)。LC-MS分析结果表明,C-J1与P-L12次生代谢产物组成中有部分产物相同,两者的差异物质主要有杨梅素、甘松新酮和2,6-二甲氧基苯酚等。结论2株逆境构树内生真菌P-L12和C-J1具有体外抑制肿瘤细胞活性,尤其是C-J1对肿瘤细胞的抑制作用较强,可作为潜在的抗肿瘤微生物药物资源。Objective To investigate the anti-tumor activity of two endophytic fungi Botryosphaeria dothidea(P-L12)and Fusarium avenaceum(C-J1)isolated from Broussonetia papyrifera in the mining area and analyze the chemical components of their metabolites.Methods Five tumour cellines in exponential growth stage were cultured in vitro,and the anti-tumor activity of the secondary metabolites of two endophytic fungi was determined by thiazolyl blue(MTT)method.After 48h of drug treatment,the cell proliferation under different conditions was measured,the 50%inhibitory concentration(ICso)of the two secondary metabolites was calculated and the trend was analyzed.The chemical components of the two endophytic fungi were analyzed by LC-MS to determine their material basis.Results The ethyl acetate extracts from the fermentation products of two endophytic fungi had inhibitory effects on five kinds of cancer cells.After 48 h of exposure,C-J1 has high cytotoxicity,the highest inhibitory effect on human hepatoma cell HepG2,ICso was(14.21±1.56)μg·mL^(-1),and also has high cytotoxicity on the other four tumor cells.The secondary metabolite of P-L12 only has a high inhibitory effect on human prostate cancer cell DU-145 with ICso(9.96±3.00)μg·mL^(-1).LC-MS analysis found that C-Jl and P-L12 had the same composition of some secondary metabolites.The difference substances between the two endophytic fungi were myricetin,mannitol and 2,6-dimethoxyphenol,etc.Conclusion The two endophytic fungi L12 and C-J1 from Broussonetia papyrifera under stress have inhibitory effects on tumor cells,especially C-J1 has high inhibitory effects on tumor cells,which might be used as a potential microbial resources for antitumor drug development.

关 键 词：构树 内生真菌 抗肿瘤活性 次生代谢产物 液相色谱-质谱联用 

分 类 号：R28[医药卫生—中药学]