Cytotoxic and apoptogenic properties of three isolated diterpenoids from Salvia chorassanica through bioassay-guided fractionation.

Bioassay-guided fractionation of Salvia chorassanica Bunge roots for the first time led to the isolation of taxodione, ferruginol and 6-hydroxysalvinolone. Cytotoxic studies revealed that all compounds exhibited high cytotoxic activity against apoptosis-proficient HL-60 and apoptosis-resistant K562 cells, with IC50 values ranging from 7.7 to 60.3 μM with much less cytotoxic effects on normal human lymphocytes. Sub-G1 peak in flow cytometry histogram of treated cells by S. chorassanica and all pure compounds in comparison with control was induced and DNA fragmentation confirmed the cytotoxicity and apoptosis. Taxodione, ferruginol and 6-hydroxysalvinolone (2.5 and 5.0 μM) also enhanced expression of the pro-apoptotic protein Bax, cleaved caspase-3 and cleaved PARP after treatment for 48 h. Collectively, these findings suggest cytotoxic and apoptotic effectiveness of taxodione, ferruginol and 6-hydroxysalvinolone against the leukemic K562 and HL-60 cancer cells.