Curcumin down regulates homeobox gene NKX3.1 in prostate cancer cell LNCaP

Zhang, Huina; Yu, Chunxiao; Zhang, Pengju; Chen, Weiwen; An-li, Jiang; Kong, Feng-Ming; Deng, Jingjing; Zhang, Jianye; Young, Charles Y.F.

doi:10.1111/j.1745-7254.2007.00501.x

Cited by 35 publications

(24 citation statements)

References 38 publications

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“…These findings are consistent with recent reports indicating similar expression changes of HO-1, ATF3 and NKX3.1 genes in response to curcumin. [17][18][19] Some of the novel targets modulated by curcumin presented in our study include TRIB3, AKAP12, TncRna, TMPRSS2, KLK2 and PMEPA1 (see Suppl. data).…”

Section: Discussionmentioning

confidence: 99%

Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome

Thangapazham¹,

Shaheduzzaman²,

Kim³

et al. 2008

Cancer Biology & Therapy

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Curcumin (diferuloylmethane) is the major active component of turmeric and is being actively investigated for its anti-cancer properties. To better understand the biological mechanisms of the chemopreventive potential of curcumin in prostate cancer, we have evaluated curcumin regulated transcriptome in prostate cancer cells. Hierarchical clustering methods and functional classification of the Curcumin-Gene Expression Response (Cu-GER) showed temporal co-regulation of genes involved in oxidative stress response and growth signaling pathways. Interestingly, C4-2B, androgen independent metastatic prostate cancer cells exhibited attenuated Cu-GER response in comparison to parental androgen dependent and less aggressive LNCaP cells. Androgen Receptor (AR) regulated genes which play critical roles in normal growth and differentiation of the prostate gland, as well as in prostate cancer, were also a part of the Cu-GER. Of note, curcumin downregulated transcript encoded by the potentially causal TMPRSS2-ERG gene fusion, a common oncogenic alteration noted in 50-70% of prostate cancer patients. Further more, expression of EGFR and ERBB2 receptor were found to be downregulated in curcumin treated LNCaP and C4-2B cells. This report for the first time establishes novel features of Cu-GER in prostate cancer cells of varying tumorigenic phenotypes and provides potentially novel read-outs for assessing effectiveness of curcumin in prostate cancer and likely in other cancers. Importantly, new gene-networks identified here further delineate molecular mechanism(s) of action of curcumin in prostate cancer cells.

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Section: Discussionmentioning

confidence: 99%

Androgen responsive and refractory prostate cancer cells exhibit distinct curcumin regulated transcriptome

Thangapazham¹,

Shaheduzzaman²,

Kim³

et al. 2008

Cancer Biology & Therapy

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“…Several analogs of curcumin were also shown to act as androgen receptor antagonists [81]. Such a downregulation of AR expression and the blockage of its DNA binding activity by curcumin lead also to the inhibition of the homeobox gene NKX3.1 [119], an androgen-regulated NK-class homeobox gene thought to play an important role in normal prostate organogenesis and carcinogenesis [14].…”

Section: Down-regulation Of the Androgen Receptors And Co-factorsmentioning

confidence: 98%

Chemopreventive potential of curcumin in prostate cancer

et al. 2009

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The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention in order to prevent or eradicate prostate malignancies. We present here an overview of the chemopreventive potential of curcumin (diferuloylmethane), a well-known natural compound that exhibits therapeutic promise for prostate cancer. In fact, it interferes with prostate cancer proliferation and metastasis development through the down-regulation of androgen receptor and epidermal growth factor receptor, but also through the induction of cell cycle arrest. It regulates the inflammatory response through the inhibition of pro-inflammatory mediators and the NF-kappaB signaling pathway. These results are consistent with this compound's ability to up-induce pro-apoptotic proteins and to down-regulate the anti-apoptotic counterparts. Alone or in combination with TRAIL-mediated immunotherapy or radiotherapy, curcumin is also reported to be a good inducer of prostate cancer cell death by apoptosis. Curcumin appears thus as a non-toxic alternative for prostate cancer prevention, treatment or co-treatment.

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“…57 As reported earlier, the expression of NKX3.1 and KLK3 (PSA) genes was found to be downregulated by curcumin. 20 The authors made two other major observations. First, curcumin downregulated the TMPSS2-ERG gene fusion, a common oncogenic alteration noted in 50-70% patients with prostate cancer.…”

Section: New Developmentsmentioning

confidence: 98%

“…Evidence has shown that metastatic prostate carcinomas also use the SDF-1/CXCR4 pathway to localize to the bone, and CXCR4 expression has been reported for various human prostate has been shown to downregulate the transactivation and expression of AR and AR-related cofactors, leading to downregulation of the homeobox gene NKX3.1, a prostate-specific gene. 19,20 Additionally, curcumin has been shown to act as an androgen receptor antagonist. 21 Curcumin also inhibits prostate-specific antigen (PSA), a critical marker of prostate cancer progression upregulated in androgen-independent prostate cancer, through the activation of NFκB.…”

Section: Why Does Curcumin Have Potential Against Prostate Cancer?mentioning

confidence: 99%

“…[19][20][21] In this issue of Cancer Biology & Therapy, Thangapazham and colleagues used an unbiased approach to examine the differences between androgen-dependent and androgen-independent prostate cancer cells in global gene expression in response to curcumin treatment. 56 They employed the less-aggressive LNCaP as an androgen-dependent line and its subclone, C4-2B, as a more aggressive, androgen-independent cell line.…”

Section: New Developmentsmentioning

confidence: 99%

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