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Planta Med 2010; 76(7): 689-693
DOI: 10.1055/s-0029-1240678
Pharmacology
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

24-Hydroxyursolic Acid from the Leaves of the Diospyros kaki (Persimmon) Induces Apoptosis by Activation of AMP-activated Protein Kinase

Prem Khanal1 [*] , Won-Keun Oh1 [*] , Phuong Thien Thuong1 , Sung Dae Cho2 , Hong Seok Choi1
  • 1BK21 Project Team, College of Pharmacy, Chosun University, Gwangju, Republic of Korea
  • 2School of Dentistry, Chonbuk National University, Jeonju, Republic of Korea
Further Information

Publication History

received Sept. 13, 2009 revised Nov. 8, 2009

accepted Nov. 11, 2009

Publication Date:
03 December 2009 (online)

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Abstract

There are multiple lines of evidence that persimmon extract and its constituents have potent antitumor activity against human cancer cells. However, the molecular mechanisms of 24-hydroxyursolic acid, a triterpenoid found in persimmon, on antitumor activities are not yet understood. Here, we demonstrate that 24-hydroxyursolic acid inhibited cell proliferation, strongly activated AMP-activated protein kinase (AMPK) and mediated critical anticancer effects by inhibition of cyclooxygenase (COX-2) expression in HT-29 cells. In addition, 24-hydroxyursolic acid induced cellular apoptosis by activation of poly(ADP-ribose) polymerase (PARP), caspase-3, and phosphorylation of p53 at Ser15. It also strongly induced DNA fragmentation in HT-29 cells and thereby significantly inhibited colony formation of HT-29 cells in soft agar. In addition, 24-hydroxyursolic acid blocked the EGF-induced ERKs phosphorylation and led to the inhibition of AP-1 activity and cell transformation in JB6 CL41 cells. Collectively, these findings are the first to reveal a molecular basis for the anticarcinogenic action of 24-hydroxyursolic acid and might account for the reported chemopreventive and chemotherapic effects of persimmon extracts.

Key words

Diospyros kaki - Ebenaceae - persimmon - 24‐hydroxyursolic acid - AMPK - COX‐2

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1 These authors contributed equally to this work.

Prof. Ph.D. Hong Seok Choi

College of Pharmacy
Chosun University

501–759 Gwangjiu

Republic of Korea

Phone: + 82 6 22 30 63 79

Fax: + 82 62 22 54 14

Email: chs@chosun.ac.kr