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.