Antiproliferative and Pro-Apoptotic Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica in Human Leukemia Cell Lines

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From: American Journal of Chinese Medicine(Vol. 43, Issue 04)
Publisher: World Scientific Publishing Co. Pte Ltd.
Document Type: Article
Length: 248 words

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To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: Byline: Takuhiro Uto, Nguyen Huu Tung, Regina Appiah-Opong, Abigail Aning, Osamu Morinaga, Dominic Edoh, Alexander K. Nyarko, Yukihiro Shoyama Alnus japonica Steud is a tree that grows in damp areas of mountain valleys and has been used as a traditional medicine in Asia. We investigated the antiproliferative activity of hirsutanone (Hir) and oregonin (Ore) in human cancer cell lines and elucidated their mechanisms of action. A cytotoxicity study using a panel of 12 human cancer and 4 normal cell lines indicated that Hir exhibited potent antiproliferative activity against 4 leukemia (Jurkat, U937, THP-1, and HL-60) and 2 colon cancer cell lines (HCT-15 and Colo205). Although Ore suppressed the cell growth of Jurkat and THP-1, its inhibitory potency was weaker than that of Hir. The IC.sub.50 values of Hir and Ore in Jurkat were 11.37 [micro]M and 22.16 [micro]M, respectively. Further analysis on Jurkat cells demonstrated that Hir caused a sequence of events involved in apoptosis, including nuclear morphological changes and accumulation of cells with sub-G1 DNA content. Hir led to the cleavage of poly(ADP-ribose) polymerase (PARP) and activation of caspase-3, -8, and -9. In addition, Hir-induced PARP cleavage was completely abolished by specific inhibitors to these caspases. Our data suggested that Hir is a potent antiproliferative compound against the 4 leukemia cell lines and the 2 colon cancer cell lines tested. Furthermore, Hir exerts antiproliferative actions via caspase-dependent apoptotic cell death.

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Gale Document Number: GALE|A461716516