Cytotoxic Indole Diterpenoids from a Sphagneticola trilobata-Derived Fungus Aspergillus sp. PQJ-1.

Two new indole diterpene derivatives, 5S-hydroxy-ß-aflatrem (1) and 14R-hydroxy-ß-aflatrem (2), along with one known analogue, 14-(N,N-dimethl-L-valyloxy)paspalinine (3), were isolated from the fermentation broth of the fungus Aspergillus sp. PQJ-1 derived from Sphagneticola trilobata. The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. All the compounds (1-3) were evaluated for their cytotoxicity against A549, Hela, Hep G2, and MCF-7 cell lines. Compounds 1 and 2 exhibited selective inhibition against Hela cells. Further studies showed that 1 significantly induced apoptosis and suppressed migration and invasion in Hela cells. Moreover, 1 could up-regulate pro-apoptotic genes BAX and Caspase-3 and down-regulate anti-apoptotic genes Bcl-xL and XIXP.