Antiproliferative and Apoptotic Activities of Linear Furocoumarins from Notopterygium incisum on Cancer Cell Lines

Bioassay-guided fractionation of the antiproliferative chloroform extract of the traditional Chinese medicine Qiang-Huo (Notopterygium incisum) led to the isolation of nine linear furocoumarins (1-9). All the isolates were tested against two human cancer cell lines (HepG-2 and MCF-7) and a rat cancer cell line (C6) using the MTT assay method. Among them, notopol (1), notopterol (2), 5-[(2E,5Z)-7-hydroxy-3,7-dimethyl-2,5-octadienoxy]psoralene (3), and 5-[(2,5)-epoxy-3-hydroxy-3,7-dimethyl-6-octenoxy]psoralene (4) showed significant antiproliferative activity against the HepG-2 and C6 cancer cell lines, with IC50 values of 7.7-24.8 mu g/mL (5-FU: ca. 5 mu g/mL). Compounds 1-3 also showed moderate cytotoxicity against the MCF-7 cancer cell line, with IC50 values of 39.4-61.3 mu g/mL (5-FU: 17.3 mu g/mL). The cell cycle-specific inhibition and apoptosis induced by compounds 1 and 2 were determined using flow cytometry. The structure-activity relationship (SAR) is briefly discussed herein. It was found that the presence of a free hydroxy at the lipophilic side chain linked to C-5 of the linear furocoumarins was essential for their in vitro antiproliferative activity.