title: Antiproliferative and Pro-Apoptotic Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica in Human Leukemia Cell Lines.
abstract: 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 IC50 values of Hir and Ore in Jurkat were 11.37 μM and 22.16 μM, 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.
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Uto
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.|School of Medicine and Pharmacy, Vietnam National University, Hanoi, Cau Giay, Hanoi, Vietnam.
authors.forename: Nguyen Huu
authors.initials: NH
authors.lastname: Tung
authors.affiliation: Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana.
authors.forename: Regina
authors.initials: R
authors.lastname: Appiah-Opong
authors.affiliation: Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana.
authors.forename: Abigail
authors.initials: A
authors.lastname: Aning
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Morinaga
authors.affiliation: Centre for Scientific Research into Plant Medicine, Mampong-Akuapem 73, Ghana.
authors.forename: Dominic
authors.initials: D
authors.lastname: Edoh
authors.affiliation: Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Nyarko
authors.affiliation: Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University, Nagasaki 859-3298, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
mesh_terms: D029661:Alnus / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D036381:Diarylheptanoids / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000473:pathology*; D024301:Plant Bark / Q000737:chemistry
chemical_list: D036381:Diarylheptanoids; D020169:Caspases
keywords: Alnus japonica; Antiproliferation; Apoptosis; Diarylheptanoid; Hirsutanone; Leukemia Cells; Oregonin