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Planta Med 2003; 69(12): 1091-1095
DOI: 10.1055/s-2003-45188
Original Paper
Pharmacology
© Georg Thieme Verlag Stuttgart · New York

Cytotoxic Activity of Coumarins from the Fruits of Cnidium monnieri on Leukemia Cell Lines

Ling-Ling Yang1 , 2 , Min-Chieh Wang1 , Lih-Geeng Chen2 , Ching-Chiung Wang1
  • 1School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan, R.O.C.
  • 2Graduate Institute of Biopharmaceutics Science, Life Science College, National Chiayi University, Chiayi, Taiwan, R.O.C.
The authors gratefully acknowledge the financial support (NSC91-2320-B-038-042) from the National Science Council, Republic of China
Further Information

Publication History

Received: May 13, 2003

Accepted: September 30, 2003

Publication Date:
29 January 2004 (online)

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Abstract

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.

Key words

Cnidium monnieri - Umbelliferae - osthol - imperatorin - HL-60 cell - apoptosis

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Prof. Associate Ching-Chiung Wang

School of Pharmacognosy

College of Pharmacy

Taipei Medical University

250 Wu-Hsing Street

Taipei 110

Taiwan, R.O.C.

Phone: +886-2-27361661 ext. 6161

Fax: +886-2-27388351

Email: crystal@tmu.edu.tw

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