Cytotoxic activity of coumarins from the fruits of Cnidium monnieri on leukemia cell lines.
Cnidii monnieri Fructus [CmF; Cnidium monnieri (L.) Cusson] is used as a tonic agent in traditional Chinese medicine. In a previous Chinese herb-cytotoxicity screening test, the ethanol extract of CmF exhibited strong effects on human leukemia (HL-60), cervical carcinoma (HeLa) and colorectal carcinoma (CoLo 205) cells. Then, the CmF extract was subjected to silica gel column chromatography and recrystallization to give five coumarins: osthol, imperatorin, bergapten, isopimpinellin, and xanthotoxin. Among these compounds, osthol showed the strongest cytotoxic activity on tumor cell lines. The structure-activity relationship established from the results indicated that the prenyl group has an important role in the cytotoxic effects. However, imperatorin showed the highest sensitivity to HL-60 cells and the least cytotoxicity to normal PBMCs. Osthol and imperatorin both caused apoptotic bodies, DNA fragmentation, and enhanced PARP degradation in HL-60 cells by biochemical analysis. These results indicate that osthol and imperatorin can induce apoptosis in HL-60 cells. Therefore, osthol and imperatorin are cytotoxic marker substances in the fruits of Cnidium monnieri.
Yang
Ling-Ling
LL
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, ROC.
Wang
Min-Chieh
MC
Chen
Lih-Geeng
LG
Wang
Ching-Chiung
CC
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000187:drug effects; D031048:Cnidium; D003374:Coumarins / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005434:Flow Cytometry; D018922:HL-60 Cells / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D003374:Coumarins; D010936:Plant Extracts