Retracted: Curcumin (diferuloylmethane) inhibits constitutive active NF‐κB, leading to suppression of cell growth of human T‐cell leukemia virus type I‐infected T‐cell lines and primary adult T‐cell leukemia cells

Abstract

Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by infection with human T-cell leukemia virus type I (HTLV-I) and remains incurable. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, can be potentially effective by promoting cell apoptosis. Here we examined whether curcumin is effective in the treatment of ATL. Curcumin prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells but not of normal peripheral blood mononuclear cells. Curcumin induced cell cycle arrest by reducing the expression of cyclin D1, Cdk1 and Cdc25C and apoptosis by reducing the expression of XIAP and survivin. Most of these genes are known to be regulated by NF-jB, which plays a critical role in oncogenesis by HTLV-I. Curcumin suppressed constitutive active NF-jB of HTLV-Iinfected T-cell lines and primary ATL cells by inhibiting phosphorylation of IjBa. Curcumin also inhibited Tax-induced NF-jB transcriptional activity. However, curcumin-induced suppression of cell growth did not correlate with Tax expression level. Curcumin inhibited the growth of HTLV-I-infected T-cell tumors implanted subcutaneously in SCID mice. Our results indicate that curcumin has tumor-suppressive activity against ATL. ' 2005 Wiley-Liss, Inc.

Resistance to apoptosis of HCW‐2 cells can be overcome by curcumin‐ or vincristine‐induced mitotic catastrophe

“…28 The direct inhibition of survivin expression by curcumin was shown very recently in adult T-cell leukemia. 8 Also our data (Wolanin et al, accepted to Mol. Cancer Res.)…”

“…It is very well known that curcumin can influence many cell functions by targeting transcriptional activities. [21][22][23] Curcumin is a well-known inhibitor of NFjB transcription factor, 8 which recently has been recognized as transcriptional activator of survivin. 24 To further support the hypothesis that survivin decrease is due to NFjB inhibition, we analyzed 2 other very well-recognized NFjB targets, namely Bcl-2 and XIAP, 25 and found that the protein level of both genes resulted to be decreased in curcumin-but not vincristine-treated cells.…”

“…5 It has been very recently shown that curcumin (diferuloylmethane), a natural dye from the rhizome of Curcuma longa and a known apoptotic inducer, downregulates survivin. 8 In other experiments, it has been shown that curcumin arrests MCF-7 cells in G 2 /M, disrupts mitotic spindle structure and induces micronucleation in MCF-7 breast cancer, 9 displaying cell morphology that fits very well to the mitotic catastrophe picture. Accordingly, we suppose that curcumin might disrupt mitotic spindle by decreasing survivin level and induce mitotic catastrophe, especially in cells with impaired DNA damage checkpoints and apoptotic signaling pathways.…”

Curcumin Affects Components of the Chromosomal Passenger Complex and Induces Mitotic Catastrophe in Apoptosis-Resistant Bcr-Abl-Expressing Cells

“…The ability of curcumin to induce cell death in various cancer cells has been reported by many groups, including ourselves (11, 12, 27-31). Interestingly, curcumin was able to suppress cell growth of human T-cell leukemia virus type I -infected T-cell lines as well as primary adult T-cell leukemia cells but not normal peripheral blood mononuclear cells (13). Although the mechanism of curcumin-induced cell death seems to be cell specific and dependent on curcumin concentration, the main reported method of cell death induced by curcumin is apoptosis.…”

“…We showed that curcumin was able to overcome apoptosis resistance in cancer cells overexpressing P-glycoprotein, multidrug resistance-associated protein 1, and heat shock protein 70 (11,12). Recently, curcumin was described as a tumor suppressive agent against adult T-cell leukemia (13). These observations indicated that curcumin may have potential in inducing cell death in apoptosis-resistant Bcr-Abl-expressing cells.…”