Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft.
Paris polyphylla is a traditional Chinese Medical herb that has been used in treating cancer for thousands of year. Without studies on the anticancer effects of Paris polyphylla being initiated before, we have first studied the component of Paris polyphylla and have spotted out a steroidal saponin, polyphyllin D. As long as the chemical structure and the improved synthesis of polyphyllin D were ascertained, both in vitro to in vivo studies were performed. It was found that treatment of MCF-7 and MDA-MB-231 cells with polyphyllin D resulted in the inhibition of viability and induction of apoptosis in a dose-dependent manner, with an IC50 of 5 microM and 2.5 microM, respectively, after 48 hours of incubations. Apoptosis of MCF-7 and MDA-MB-231 cells by polyphyllin D was evidenced by the occurrence of DNA fragmentation, formation of a hypodiploid peak in the cell cycle analysis, phosphatidyl-serine externalization and a late loss of membrane integrity. Mechanistically, polyphyllin D dissipates the mitochondrial membrane potential, induces a downregulation of anti-apoptotic Bcl-2 expression and an up-regulation of pro-apoptotic Bax expression, and activates caspase-9. These results suggest that polyphyllin D elicits apoptosis through mitochondria dysfunction. In vivo study demonstrated that daily administration of polyphyllin D (2.73 mg/kg body weight) through intravenous injection for ten days in nude mice bearing MCF-7 cells effectively reduced tumor growth for 50% in terms of tumor weight and size, given no significant toxicity in heart and liver to the host. All these findings provide novel insights that polyphyllin D could serve as a candidate in breast cancer treatment.
Lee
Mei-Sze
MS
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
Yuet-Wa
Judy Chan
JC
Kong
Siu-Kai
SK
Yu
Biao
B
Eng-Choon
Vincent Ooi
VO
Nai-Ching
Henry Wong
HW
Chung-Wai
Thomas Mak
TM
Fung
Kwok-Pui
KP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D012503:Saponins; C121203:polyphyllin D; D004144:Diosgenin