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Planta Med 2008; 74(2): 151-155
DOI: 10.1055/s-2008-1034286
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Growth Inhibition and G1 Cell Cycle Arrest Mediated by 25-Methoxyhispidol A, a Novel Triterpenoid, Isolated from the Fruit of Poncirus trifoliata in Human Hepatocellular Carcinoma Cells

Ji- Young Hong1 , Hye-Young Min1 , Guang Hua Xu2 , Jong-Gu Lee2 , Seung-Ho Lee2 , Young Shik Kim3 , Sam Sik Kang3 , Sang Kook Lee1
  • 1College of Pharmacy, Ewha Womans University, Seoul, Korea
  • 2College of Pharmacy, Yeungnam University, Kyongsan, Korea
  • 3Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea
Further Information

Publication History

Received: September 13, 2007 Revised: November 25, 2007

Accepted: November 27, 2007

Publication Date:
24 January 2008 (online)

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Abstract

Poncirus trifoliata (Rutaceae) extracts have been known to possess anti-allergic, anti-inflammatory and antiviral activities. However, other biological activities, especially, the anticancer potential of extracts of P. trifoliata or its constituents, have not been fully investigated yet. In this study, we have evaluated the antiproliferative effects of a novel triterpenoid, 25-methoxyhispidol A, isolated from the fruit of P. trifoliata against SK-HEP-1 human hepatocellular carcinoma cells. Flow cytometric analysis indicated that 25-methoxyhispidol A arrests the cell cycle in the G1 phase at the earlier time and subsequently induces apoptosis of the cancer cells. Further study revealed that the cell cycle arrest in the G1 phase by 25-methoxyhispidol A correlated well with the inhibition of phosphorylation of the retinoblastoma (Rb) protein, and with the down-regulation of cyclin D1 and cyclin-dependent kinase cdk4 and the induction of cdk inhibitor p21WAF1/Cip1 protein. These findings suggest the potential of 25-methoxyhispidol A isolated from the fructus of P. trifoliata as an antitumor agent against human hepatocarcinoma cells by arresting the cell cycle and inducing apoptosis.

Key words

25-Methoxyhispidol A - Poncirus trifoliata (L.) Raf. - Rutaceae - SK-HEP-1 cells - cell growth inhibition

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Prof. Dr. Sang Kook Lee

College of Pharmacy

Ewha Womans University

11-1 Daehyun-dong

Seodaemun-ku

Seoul 120-750

Korea

Phone: +82-2-3277-3023

Fax: +82-2-3277-2851

Email: sklee@ewha.ac.kr