%0 Journal Article %T Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells %A Yun-Hee Rhee %A Soo-Jin Jeong %A Hyo-Jeong Lee %A Hyo-Jung Lee %A Wonil Koh %A Ji Jung %A Sun-Hee Kim %A Kim Sung-Hoon %J BMC Cancer %D 2012 %I BioMed Central %R 10.1186/1471-2407-12-28 %X Despite weak cytotoxicity against U266 cells, EP suppressed phosphorylation, DNA binding activity and nuclear translocalization of signal transducer and activator of transcription 3 (STAT3) in U266 cells at nontoxic concentrations. Also, EP inhibited phosphorylation of the upstream kinases Janus kinase 2 (JAK2) and Src in a time-dependent manner. Furthermore, EP increased the expression of protein tyrosine phosphatase SHP-1 at protein and mRNA levels, and conversely silencing of the SHP-1 gene clearly blocked EP-mediated STAT3 inactivation. In addition, EP significantly decreased vascular endothelial growth factor (VEGF), one of STAT3 target genes at cellular and protein levels as well as disrupted in vitro tube formation assay. Moreover, EP significantly suppressed the growth of U266 cells inoculated in female BALB/c athymic nude mice and immunohistochemistry revealed that EP effectively reduced the expression of STAT3 and CD34 in tumor sections compared to untreated control.These findings suggest that EP can exert antitumor activity in multiple myeloma U266 cells partly with antiangiogenic activity targeting JAK2/STAT3 signaling pathway as a potent cancer preventive agent for treatment of multiple myeloma cells.Ergosterol Peroxide (EP), 5¦Á, 8¦Á-epidioxy-22E-ergosta-6, 22-dien-3¦Â-ol, is found in plants [1], lichens [2] and mushrooms such as Ganoderma lucidum [3], Sporothrix schenckii [4] and Cordyceps sinensis [5]. Despite various biological effects of EP such as immunosuppressive [6-8], anti-viral [9], anti-inflammatory [10] and anti-tumor [5,10] activities, the underlying molecular mechanisms for anti-cancer activity of EP still remain unclear.STAT proteins originally discovered as latent cytoplasmic transcription factors [11] are involved in a variety of cellular processes such as cell proliferation, differentiation and apoptosis [12,13]. Of the STAT proteins, STAT3 is often constitutively activated in many human cancer cells including multiple myeloma, leukemia, %K ergosterol peroxide %K JAK2 %K STAT3 %K angiogenesis %K multiple myeloma %U http://www.biomedcentral.com/1471-2407/12/28