TY - JOUR
T1 - Antiproliferative and Pro-Apoptotic Activity of Diarylheptanoids Isolated from the Bark of Alnus japonica in Human Leukemia Cell Lines
AU - Uto, Takuhiro
AU - Tung, Nguyen Huu
AU - Appiah-Opong, Regina
AU - Aning, Abigail
AU - Morinaga, Osamu
AU - Edoh, Dominic
AU - Nyarko, Alexander K.
AU - Shoyama, Yukihiro
N1 - Publisher Copyright:
© 2015 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
KW - Alnus japonica
KW - Antiproliferation
KW - Apoptosis
KW - Diarylheptanoid
KW - Hirsutanone
KW - Leukemia Cells
KW - Oregonin
UR - http://www.scopus.com/inward/record.url?scp=84938414913&partnerID=8YFLogxK
U2 - 10.1142/S0192415X15500470
DO - 10.1142/S0192415X15500470
M3 - Article
C2 - 26119959
AN - SCOPUS:84938414913
SN - 0192-415X
VL - 43
SP - 757
EP - 767
JO - American Journal of Chinese Medicine
JF - American Journal of Chinese Medicine
IS - 4
ER -