中华剑角蝗共生真菌Penicillium oxalicum中抗肿瘤次级代谢产物研究

The Study of Antitumor Secondary Metabolites from Penicillium oxalicum,a Fungus Residingin Acrida cinerea

采用活性追踪法,从中华剑角蝗肠道共生真菌Penicillium oxalicum的发酵产物中分离得到一个具有较高抗肿瘤活性的苯并吡喃酮二聚体类化合物,经波谱数据及理化性质鉴定为secalonic acid A,为首次从该属菌种中分离得到。Secalonic acid A对多种肿瘤细胞如人肝癌细胞(HepG2)、人肺癌细胞(A549)、人宫颈癌细胞(Ca Ski)、鼻咽癌细胞(CNE2)和人乳腺癌细胞(MDA-MB-231)均有显著的生长抑制作用,IC50值分别为1.12、2.23、4.16、20.18和22.65μM,但对正常细胞如人永生化表皮细胞(HaCAT)和犬肾细胞(MDCK)的细胞毒性较小,IC50值大于100μM,具有一定的选择性。流式细胞仪检测表明,Secalonic acid A能有效诱导HepG2细胞凋亡,早期凋亡率最高达到40.6%,并能有效破坏HepG2细胞的线粒体膜电位,相对破坏率最高达到97.3%。提示该化合物可能通过线粒体途径诱导肿瘤细胞发生凋亡而发挥抗肿瘤作用。

A dimerlc naphthopyrones were activity-guided isolated by M＇IT method from the fermentation broth extract of Penicillium o＇xalicum, a fungus residing in Acrida cinerea. On the basis of spectral data and physicochemieal properties, it was identified as secalonic acid A that isolated for the first time from the endophytic fungus of Penicillium oxalicum. Secalonie acid A showed significant cytotoxicity to several human cancer cell lines such as HepG2, A549, Ca Ski, CNE2, MDA-MB-231 with IC5o values of 1.12,2.23,4. 16,20.18,22.65 μM,but slightly cytotoxicity to normal cell lines such as HaCAT and MDCK with IC50 values greater than 100μM. Flow cytometry assay confirmed that secalonic acid A caused a dose-dependent early apoptotie effect with a hlghest-level of 40.6%. Furthermore, secalonic acid A triggered a rapid decrease of the mitochondrial membrane potential by 97.3% relatively. These findings suggested that secalonie acid A induced mitochondrial-mediatod apoptosis in HepG cells.