Cytotoxic and pro-apoptotic activities of cynaropicrin, a sesquiterpene lactone, on the viability of leukocyte cancer cell lines.
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.
Cho
Jae Youl
JY
School of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, 192-1, Hyoja2-Dong, Chuncheon, Kangwon-Do 200-701, South Korea. jaecho@kangwon.ac.kr
Kim
Ae Ra
AR
Jung
Jee H
JH
Chun
Taehoon
T
Rhee
Man Hee
MH
Yoo
Eun Sook
ES
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005434:Flow Cytometry; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects* / Q000473:pathology; D008858:Microscopy, Phase-Contrast; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007783:Lactones; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D007770:L-Lactate Dehydrogenase; C087857:protein kinase C gamma; D011493:Protein Kinase C; C075687:cynaropicrin