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Triterpenoid cucurbitacins have been shown to have antitumor activity, but the mechanism of this activity is not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>The effects of cucurbitacin D on the proliferation and apoptotic induction of T\u2010cell leukemia cells using the Cell viability assay and Annexin V staining were evaluated. To investigate the mechanisms of apoptosis, antiapoptotic protein, NF\u2010\u03baB, and the proteasome activity of leukemia cells treated with cucurbitacin D were evaluated by Western blotting both in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>In this study, cucurbitacin D was found to inhibit proliferation and to induce apoptosis of T\u2010cell leukemia cells. Constitutively activated NF\u2010\u03baB was inhibited by cucurbitacin D in the nucleus, which resulted in accumulation of NF\u2010\u03baB in the cytoplasm, leading to down\u2010regulation of the expression of antiapoptotic proteins Bcl\u2010xL and Bcl\u20102. Furthermore, cucurbitacin D induced the accumulation of inhibitor of NF\u2010\u03baB (I\u03baB)\u03b1 by inhibition of proteasome activity. Low doses of cucurbitacin D synergistically potentiated the antiproliferative effects of the histone deacetylase inhibitor VPA. Finally, the proapoptotic and proteasome inhibitory activities of cucurbitacin D also were demonstrated using SCID mice in an in vivo study.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>Cucurbitacin D induced apoptosis through suppression of proteasome activity both in vitro and in vivo, making cucurbitacin D a promising candidate for clinical applications in the treatment of T\u2010cell leukemia. Cancer 2011;. \u00a9 2010 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.25711","type":"journal-article","created":{"date-parts":[[2010,12,23]],"date-time":"2010-12-23T15:11:25Z","timestamp":1293117085000},"page":"2735-2746","source":"Crossref","is-referenced-by-count":34,"title":["Apoptosis induction through proteasome inhibitory activity of cucurbitacin D in human T\u2010cell 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