The antitumoral effect of Paris Saponin I associated with the induction of apoptosis through the mitochondrial pathway.
Rhizoma Paridis, a traditional Chinese medicine, has shown promise in cancer prevention and therapy. In the present study, we isolated Paris Saponin I (PSI), an active component of Rhizoma paridis, and evaluated its effects on a panel of human cell lines and in a mouse model of human ovarian cancer to explore the mechanisms of its activity. PSI had more potent and selective cytotoxic effects on tumor cell lines than etoposide had, promoting dramatic G(2)-M phase arrest and apoptosis in SKOV3 cells in a time- and dose-dependent manner. Furthermore, PSI treatment increased levels of Bax, cytochrome c, activated caspase-3, active caspase-9, and cleaved poly(ADP-ribose) polymerase and decreased both Bcl-2 expression levels and extracellular signal-regulated kinase-1/2 activity. We also assessed the antitumor efficacy of i.p. and p.o. PSI administration in mice bearing SKOV3 tumors; both significantly inhibited the growth of SKOV3 cells in a subcutaneous xenograft mouse model (by 66% and 52%, respectively). These results indicate that PSI mediates its effects via mitochondrial apoptosis, mitogen-activated protein kinase pathways, and G(2)-M cell cycle arrest. Most important, the efficacy of PSI in xenografts when administered p.o. or i.p. suggests its clinical potential. Thus, PSI is a potent antitumor compound and should be developed as a natural agent for cancer therapy.
Xiao
Xue
X
Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Bai
Peng
P
Bui Nguyen
Tri M
TM
Xiao
Jianguo
J
Liu
Shanling
S
Yang
Gong
G
Hu
Lina
L
Chen
Xinlian
X
Zhang
Xuemei
X
Liu
Jinsong
J
Wang
He
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction; D023041:Xenograft Model Antitumor Assays
D012503:Saponins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases