Ophiobolin A, a novel apoptosis-inducing agent from fungus strain f-7438

We isolated ophiobolin A from the f-7438 fungus strain. In the L1210 cell line, ophiobolin A (0.01-1 μM) showed cytotoxicity in a concentration-dependent manner. Morphological observations revealed that ophiobolin A (1 μM) induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. Moreover, in DNA gel electrophoretic experiments, a typical apoptotic DNA ladder pattern was observed after treatment with this compound. The flow cytometric experiment indicated that ophiobolin A (0.01-1 μM) caused a concentration-dependent apoptosis in close agreement with concentrations that induced cytotoxicity in L1210 cells. The results suggested that ophiobolin A caused the death of L1210 cells through the apoptotic process. Ophiobolin A may become a powerful pharmacological tool for studying the apoptotic mechanism.