Inhibition of STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of ergosterol peroxide in U266 multiple myeloma cells

• Main Authors: Rhee Yun-Hee, Jeong Soo-Jin, Lee Hyo-Jeong, Lee Hyo-Jung, Koh Wonil, Jung Ji, Kim Sun-Hee, Sung-Hoon Kim
• Format: Article
• Language: English
• Published: BMC 2012-01-01
• Series: BMC Cancer
• Subjects: ergosterol peroxide; JAK2; STAT3; angiogenesis; multiple myeloma
• Online Access: http://www.biomedcentral.com/1471-2407/12/28

<p>Abstract</p> <p>Background</p> <p>Ergosterol peroxide (EP) derived from edible mushroom has been shown to exert anti-tumor activity in several cancer cells. In the present study, anti-angiogenic activity of EP was investigated with the underlying molecular mechanisms in human multiple myeloma U266 cells.</p> <p>Results</p> <p>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 <it>in vitro </it>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.</p> <p>Conclusion</p> <p>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.</p>