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http://dx.doi.org/10.4062/biomolther.2012.20.3.273

Hesperidin Induces Apoptosis by Inhibiting Sp1 and Its Regulatory Protein in MSTO-211H Cells  

Lee, Kyung-Ae (Department of Biochemistry, College of Medicine, Soonchunhyang University)
Lee, Sang-Han (Department of Biochemistry, College of Medicine, Soonchunhyang University)
Lee, Yong-Jin (Soonchunhyung Environmental Health Center for Asbestos-Related Disease, College of Medicine, Soonchunhyang University Cheonan Hospital)
Baeg, Seung-Mi (Department of Biochemistry, College of Medicine, Soonchunhyang University)
Shim, Jung-Hyun (Department of Biochemistry, College of Medicine, Soonchunhyang University)
Publication Information
Biomolecules & Therapeutics / v.20, no.3, 2012 , pp. 273-279 More about this Journal
Abstract
Hesperidin, a flavanone present in citrus fruits, has been studied as potential therapeutic agents that have anti-tumor activity and apoptotic effects in several cancers, but there is no report about the apoptotic effect of hesperidin in human malignant pleural mesothelioma through the specificity protein 1 (Sp1) protein. We investigated whether hesperidin inhibited cell growth and regulated Sp1 target proteins by suppressing the levels of Sp1 protein in MSTO-211H cells. The $IC_{50}$ value of hesperidin was determined to be 152.3 ${\mu}M$ in MSTO-211H cells for 48 h. Our results suggested that hesperidin (0-160 ${\mu}M$) decreased cell viability, and induced apoptotic cell death. Hesperidin increased Sub-$G_1$ population in MSTO-211H cells. Hesperidin significantly suppressed mRNA/protein level of Sp1 and modulated the expression level of the Sp1 regulatory protein such as p27, p21, cyclin D1, Mcl-1, and survivin in mesothelioma cells. Also, hesperidin induced apoptotic signaling including: cleavages of Bid, caspase-3, and PARP, upregulation of Bax, and down-regulation of Bcl-$_{xl}$ in mesothelioma cells. These results show that hesperidin suppressed mesothelioma cell growth through inhibition of Sp1. In this study, we demonstrated that Sp1 acts as a novel molecular target of hesperidin in human malignant pleural mesothelioma.
Keywords
Rotavirus; Hepatitis A virus; Recombinant chimera protein;
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