angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer targeting vegf-vegfr signalingangiopreventive功效的纯flavonolignans水飞蓟提取物对前列腺癌靶向vegf-vegfr信号.pdfVIP

Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling 1,2 1 1 1 1 Gagan Deep , Subhash Chander Gangar , Subapriya Rajamanickam , Komal Raina , Mallikarjuna Gu , 1,2 3 1,2 Chapla Agarwal , Nicholas H. Oberlies , Rajesh Agarwal * 1 Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, Colorado, United States of America, 2 University of Colorado Cancer Center, University of Colorado Denver, Aurora, Colorado, United States of America, 3 Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America Abstract The role of neo-angiogenesis in prostate cancer (PCA) growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberrant angiogenesis through non-toxic phytochemicals could be an attractive angiopreventive strategy against PCA. The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically active constituents in Milk Thistle extract. Results showed that oral feeding of these flavonolignans (50 and 100 mg/kg body weight) effectively inhibit the growth of advanced human PCA DU145 xenografts. Immunohistochemical analyses revealed that these flavono