| First Author | Hahm ER | Year | 2013 |
| Journal | J Natl Cancer Inst | Volume | 105 |
| Issue | 15 | Pages | 1111-22 |
| PubMed ID | 23821767 | Mgi Jnum | J:199457 |
| Mgi Id | MGI:5502809 | Doi | 10.1093/jnci/djt153 |
| Citation | Hahm ER, et al. (2013) Metabolic alterations in mammary cancer prevention by withaferin a in a clinically relevant mouse model. J Natl Cancer Inst 105(15):1111-22 |
| abstractText | BACKGROUND: Efficacy of withaferin A (WA), an Ayurvedic medicine constituent, for prevention of mammary cancer and its associated mechanisms were investigated using mouse mammary tumor virus-neu (MMTV-neu) transgenic model. METHODS: Incidence and burden of mammary cancer and pulmonary metastasis were scored in female MMTV-neu mice after 28 weeks of intraperitoneal administration with 100 microg WA (three times/week) (n = 32) or vehicle (n = 29). Mechanisms underlying mammary cancer prevention by WA were investigated by determination of tumor cell proliferation, apoptosis, metabolomics, and proteomics using plasma and/or tumor tissues. Spectrophotometric assays were performed to determine activities of complex III and complex IV. All statistical tests were two-sided. RESULTS: WA administration resulted in a statistically significant decrease in macroscopic mammary tumor size, microscopic mammary tumor area, and the incidence of pulmonary metastasis. For example, the mean area of invasive cancer was lower by 95.14% in the WA treatment group compared with the control group (mean = 3.10 vs 63.77mm(2), respectively; difference = -60.67mm(2); 95% confidence interval = -122.50 to 1.13mm(2); P = .0536). Mammary cancer prevention by WA treatment was associated with increased apoptosis, inhibition of complex III activity, and reduced levels of glycolysis intermediates. Proteomics confirmed downregulation of many glycolysis-related proteins in the tumor of WA-treated mice compared with control, including M2-type pyruvate kinase, phospho glycerate kinase, and fructose-bisphosphate aldolase A isoform 2. CONCLUSIONS: This study reveals suppression of glycolysis in WA-mediated mammary cancer prevention in a clinically relevant mouse model. |
