Cynaropicrin, a
sesquiterpene lactone from Saussurea lappa, has been reported to possess immunomodulatory effects on
cytokine release,
nitric oxide production and immunosuppressive effects. In this study, we have examined cytotoxic effect of
cynaropicrin against several types of cell lines such as macrophages, eosinophils, fibroblasts and lymphocytes.
Cynaropicrin potently inhibited the proliferation of leukocyte
cancer cell lines, such as U937, Eol-1 and Jurkat T cells, but some other cells such as Chang liver cells and human fibroblast cell lines were not strongly suppressed by
cynaropicrin treatment. The cytotoxic effect of
cynaropicrin was due to inducing apoptosis and cell cycle arrest at G1/S phase, according to flow-cytometric, DNA fragmentation and morphological analyses using U937 cells. Evidence that combination treatment with
l-cysteine and
N-acetyl-l-cysteine,
reactive oxygen species scavengers, or
rottlerin (1-[6-[(3-acetyl-2,4,6-trihydroxy-5-methylphenyl)methyl]-5,7-dihydroxy-2, 2-dimethyl-2H-1-
benzopyran-8-yl]-3-phenyl-2-propen-1-one), a specific
protein kinase (PK) Cdelta inhibitor, abolished
cynaropicrin-mediated cytotoxicity and morphological change, and that
cynaropicrin-induced proteolytic cleavage of PKCdelta suggests that
reactive oxygen species and PKCdelta may play an important role in mediating pro-apoptotic activity by
cynaropicrin. Taken together, these results indicate that
cynaropicrin may be a potential
anticancer agent against some leukocyte
cancer cells such as
lymphoma or
leukemia, through pro-apoptotic activity.