1. Natural product ginsenoside 25-OCH3-PPD inhibits breast cancer growth and metastasis through down-regulating MDM2
- Author
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Wei Wang, Ruiwen Zhang, Subhasree Nag, Jiang-Jiang Qin, Ming-Hai Wang, Sukesh Voruganti, Hui Wang, and Xu Zhang
- Subjects
Time Factors ,Ginsenosides ,Transcription, Genetic ,Cancer Treatment ,lcsh:Medicine ,Gene Expression ,Pharmacology ,Biochemistry ,Metastasis ,Mice ,0302 clinical medicine ,Cell Movement ,Molecular Cell Biology ,Drug Discovery ,Basic Cancer Research ,Medicine ,Neoplasm Metastasis ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,Cell Death ,Protein Stability ,Plant Biochemistry ,Obstetrics and Gynecology ,Cell migration ,Proto-Oncogene Proteins c-mdm2 ,3. Good health ,Gene Expression Regulation, Neoplastic ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Female ,Research Article ,Drugs and Devices ,Drug Research and Development ,Down-Regulation ,Mice, Nude ,Antineoplastic Agents ,Breast Neoplasms ,03 medical and health sciences ,Breast cancer ,In vivo ,Cell Line, Tumor ,Breast Cancer ,Animals ,Humans ,Biology ,030304 developmental biology ,Cell Proliferation ,Biological Products ,Dose-Response Relationship, Drug ,Cell growth ,business.industry ,lcsh:R ,Tetracycline ,Chemotherapy and Drug Treatment ,medicine.disease ,Xenograft Model Antitumor Assays ,Cell culture ,Apoptosis ,Cancer cell ,lcsh:Q ,business - Abstract
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-3β, 12β, 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.
- Published
- 2012