Effects of polyphyllin D, a steroidal saponin inParis Polyphylla, in growth inhibition of human breast cancer cells and in xenograft

Abstract

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.

A review of connectivity map and computational approaches in pharmacogenomics

“…Interestingly, the extracts of the Paris polyphylla plant, containing polyphyllin D, have been long used in traditional Chinese medicine for cancer treatment [72]. Their CMap analysis indicated that polyphyllin D is a trigger for estrogen receptorinduced apoptosis and mitochondria-mediated apoptotic pathways [73].…”

Mitochondrial regulation of epigenetics and its role in human diseases

“…Indeed tumor-specific changes in the mtDNA copy number have been reported in human cancers. 12,[15][16][17][18][19][20] Additionally, mtDNA dimers 21 and mtDNA mutations in mitochondrial genes have been found in patients with leukemia, lung cancer, renal cell carcinoma, hepatocellular carcinoma, breast cancer and ovarian cancer. 2,3,13 Interactions between proteins encoded by mitochondrial and nuclear genomes play critical roles in cellular function.…”

Paris Polyphylla Smith: An Important High Value Himalayan Medicinal Herb

“…Steroidal saponins of P. polyphylla i.e., Polyphyllin D could serve as an agent for breast cancer treatment (Lee et al, 2005). 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.…”