Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells.
In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl alpha-L-rhamnopyranosyl-(1-->2)-(alpha-L-arabinofuranosyl)-(1-->4)]-[beta-D-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb Paris polyphylla. It has been used to treat liver cancer in China for many years. We evaluated the cell-killing mechanisms of this compound in R-HepG2 and its parental cells. The mitochondrial apoptotic pathway was found to be involved in the PD-induced apoptosis because PD elicited depolarization of mitochondrial transmembrane potential (DeltaPsim), generation of H2O2, as well as release of cytochrome c and apoptosis-inducing factor in a dose- and time-dependent manner. In conclusion, we show for the first time that PD is a potent anticancer agent that can overcome drug resistance in R-HepG2 cells and elicit programmed cell death via mitochondrial dysfunction.
Cheung
Jenny Yuen-Nei
JY
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Ong
Rose Chik-Ying
RC
Suen
Yick-Keung
YK
Ooi
Vincent
V
Wong
Henry Nai-Ching
HN
Mak
Thomas Chung-Wai
TC
Fung
Kwok-Pui
KP
Yu
Biao
B
Kong
Siu-Kai
SK
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051033:Apoptosis Inducing Factor; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005420:Flavoproteins / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012503:Saponins
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D005420:Flavoproteins; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D012503:Saponins; C121203:polyphyllin D; D045304:Cytochromes c; D004144:Diosgenin