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

• Published in: Food and chemical toxicology 2013-07, Vol.57, p.346-351
• Main Authors: Tayarani-Najaran, Zahra, Mousavi, Seyed Hadi, Tajfard, Faezeh, Asili, Javad, Soltani, Saba, Hatamipour, Mahdi, Emami, Seyed Ahmad
• Format: Article
• Language: English
• Subjects: 6-Hydroxysalvinolone; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; bcl-2-Associated X Protein - metabolism; Biological and medical sciences; Caspase 3 - metabolism; Chemical Fractionation - methods; Diterpenes - chemistry; Diterpenes - isolation & purification; Diterpenes - pharmacology; Diterpenes, Abietane - isolation & purification; Diterpenes, Abietane - pharmacology; Drug Screening Assays, Antitumor; Ferruginol; Hematologic and hematopoietic diseases; HL-60 Cells - drug effects; Humans; Inhibitory Concentration 50; K562 Cells - drug effects; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Leukemic cell lines; Medical sciences; Poly(ADP-ribose) Polymerases - metabolism; Salvia; Salvia - chemistry; Salvia chorassanica; Taxodione; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2013.03.037

•The isolation of taxodione, ferruginol and 6-hydroxysalvinolone from roots of Salvia chorassanica is reported.•High cytotoxic effects on HL-60 and K562 cells were observed.•Sub-G1 peak in flow cytometry histogram, and DNA fragmentation confirmed apoptosis.•After 48h, the expression of the pro-apoptotic protein Bax was increased and caspase-3 and PARP cleaved. 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 60.3μM 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 5.0μM) also enhanced expression of the pro-apoptotic protein Bax, cleaved caspase-3 and cleaved PARP after treatment for 48h. Collectively, these findings suggest cytotoxic and apoptotic effectiveness of taxodione, ferruginol and 6-hydroxysalvinolone against the leukemic K562 and HL-60 cancer cells.