IndraLab

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"To prove that curcumin can inhibit CSN5, we applied curcumin to multiple HCC cell lines."

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"Second, curcumin inhibits CSN5 associated kinase activity and, therefore, curcumin can inhibit pre-existing CSN5 activity in cancer cells as it can significantly reduce 4T1 tumor growth under natural conditions."

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"Further, COP9 signalosome 5 (CSN5) stabilized programmed cell death-ligand-1 (PD-L1) plays important role in TNF-α-induced cancer immunosuppression in TME, and curcumin can inhibit CSN5, leading to sensitization of cancer cells to immunotherapy [111]."

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"Curcumin inhibits deubiquitinase CSN5 to promote PD-L1 ubiquitination degradation (Lim et al., 2016)."

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"Blockade of CSN5 by curcumin destabilized PD-L1 and sensitized cancer to immunotherapy [XREF_BIBR]."

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"CSN5 associated kinase activity could be inhibited by curcumin, the treatment with which in mice bearing 4T1 tumors slowed tumor growth, increased tumor free survival, and increased IFNgamma+ CD8+ T cells when combined with CTLA-4 blockade."

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"Inhibition of CSN5 by curcumin was shown to destabilize PD-L1 resulting in diminished PD-L1 expression in various cancer cells thereby enhancing anti-tumor immunity (Figure 2)."

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"Curcumin inhibited CSN5 activity and thereby attenuated immunosuppressive response induced by PD-L1 during chronic inflammation."

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"Furthermore, inhibition of CSN5 by curcumin sensitizes inflammation-induced tumors to anti-CTLA4 therapy in various murine tumor models [38]."

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"Curcumin can inhibit the activity of CSN5 in various types of cancer and suppress TNF-α-induced PD-L1 stability in cancer cells (Uhle et al., 2003)."

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"Of note, curcumin, but not many other anticancer drugs, induces p53 predominantly by promoting CSN5 degradation [XREF_BIBR, XREF_BIBR]."

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"Curcumin inhibits CSN5 activity to promote the ubiquitination-mediated degradation of PD-L1(13)."

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"Further , COP9 signalosome 5 ( CSN5 ) stabilized programmed cell death-ligand-1 ( PD-L1 ) plays important role in TNF-alpha-induced cancer immunosuppression in TME , and curcumin can inhibit CSN5 , leading to sensitization of cancer cells to immunotherapy [ 111 ] ."

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"We show that curcumin, an important inhibitor of CSN associated kinases, can downregulate not only CSN5 but also MDM2, which results in p53 stabilization."

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"Taken together, we propose that CSN5 down-regulation by curcumin is responsible for giving rise to a rapid p53 protein accumulation without significant activation of intrinsic transcriptional activity of this transcriptional factor, implying a special significance for CSN5 controlled p53 in human cellular response to curcumin."

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"TAM-mediated secretion of TNF-α activates IKKβ/NF-κB/CSN5 signaling to increase PD-L1 levels, while curcumin suppresses this effect by counteracting CSN5-related kinase activity [54, 55] (Fig. 1)."

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"Curcumin, which has been shown to inhibit CSN5 associated kinase activity, inhibited not only CSN5 activity in a dose dependent manner in vitro (XREF_SUPPLEMENTARY) but also TNF-alpha-induced PD-L1 stabilization in cells from different types of cancers, including breast, colon, and lung cancer, and melanoma (XREF_FIG and XREF_SUPPLEMENTARY)."

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"Curcumin treatment triggered CSN5 degradation, p53 accumulation, and p62 down-regulation concomitantly at 6 h in HCT116 wt and HT29 cells, respectively, but the same CSN5 down-regulation failed to alter p62 in p53-null HCT116 p53-/- cells."

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"In addition, curcumin did not inhibit tumor growth of CSN5 knockout 4T1 cells in mice (XREF_FIG), suggesting that curcumin mediated tumor growth inhibition may be attributed primarily to CSN5 dependent regulation."

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"Li et al. have generated a water-soluble polyethylene glycol-conjugated curcumin that inhibits pancreatic cancer cell proliferation by activating Jab1/CSN5."

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"Curcumin, a small molecule compound, has been reported to inhibit CSN5-associated deubiquitination kinase activity [ 15 , 20 ]."