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Although ginseng and related herbs have a long history of utility for various health benefits, their application in cancer therapy and underlying mechanisms of action are not fully understood. Our recent work has shown that 20(S)-25-methoxyl-dammarane-3 β , 12 β , 20-triol (25-OCH 3 -PPD), a newly identified ginsenoside from  Panax notoginseng , exerts activities against a variety of cancer cells  in vitro  and  in vivo . This study was designed to investigate its anti-breast cancer activity and the underlying mechanisms of action. We observed that 25-OCH 3 -PPD decreased the survival of breast cancer cells by induction of apoptosis and G1 phase arrest and inhibited the growth of breast cancer xenografts  in vivo . We further demonstrated that, in a dose- and time-dependent manner, 25-OCH 3 -PPD inhibited MDM2 expression at both transcriptional and post-translational levels in human breast cancer cells with various p53 statuses (wild type and mutant). Moreover, 25-OCH 3 -PPD inhibited  in vitro  cell migration, reduced the expression of epithelial-to-mesenchymal transition (EMT) markers, and prevented  in vivo  metastasis of breast cancer. In summary, 25-OCH 3 -PPD is a potential therapeutic and anti-metastatic agent for human breast cancer through down-regulating MDM2. Further preclinical and clinical development of this agent is warranted.

Natural Product Ginsenoside 25-OCH3-PPD Inhibits Breast Cancer Growth and Metastasis through Down-Regulating MDM2