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-[(2 E,5 Z)-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 IC(50) values of 7.7-24.8 microg/mL (5-FU: ca. 5 microg/mL). Compounds 1- 3 also showed moderate cytotoxicity against the MCF-7 cancer cell line, with IC(50) values of 39.4-61.3 microg/mL (5-FU: 17.3 microg/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.
Wu
Shi-Biao
SB
Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai, P R China.
Pang
Fei
F
Wen
Ying
Y
Zhang
Hong-Feng
HF
Zhao
Zheng
Z
Hu
Jin-Feng
JF
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D019661:Apiaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D051381:Rats; D027343:Rhizome; D013329:Structure-Activity Relationship
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D011564:Furocoumarins