Galiellalactone is a novel therapeutic candidate against hormone‐refractory prostate cancer expressing activated Stat3

Hellsten, Rebecka; Johansson, Martin; Dahlman, Anna; Dizeyi, Nishtman; Sterner, Olov; Bjartell, Anders

doi:10.1002/pros.20699

Cited by 74 publications

(79 citation statements)

References 47 publications

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“…This demonstrates that galiellalactone is not specific for STAT3, although the identification of STAT3 as a direct binding target correlates well with the inhibitory effects seen in galiellalactone-treated DU145 cells expressing constitutively active STAT3. In addition, galiellalactone has been shown to be well tolerated in animal studies with repeat dosing and displays minimal cytotoxic effects in non-STAT3-dependent cells, which would not be expected with a non-discriminate and highly reactive compound (20).…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that galiellalactone inhibits the growth, both in vitro and in vivo, of prostate cancer cells expressing activated STAT3 and inhibits the expression of STAT3-regulated genes and proteins (20). Furthermore, galiellalactone inhibits growth and induces apoptosis of prostate cancer stem cell-like cells expressing phosphorylated STAT3 (pSTAT3) (21).…”

mentioning

confidence: 99%

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Galiellalactone Is a Direct Inhibitor of the Transcription Factor STAT3 in Prostate Cancer Cells

Don‐Doncow

Escobar

Johansson

et al. 2014

Journal of Biological Chemistry

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Background: STAT3 is constitutively active in castration-resistant prostate cancer and the fungal metabolite galiellalactone inhibits STAT3 signaling. Results: Galiellalactone binds covalently to one or more cysteines in STAT3 and prevents STAT3 binding to DNA. Conclusion: Galiellalactone inhibits STAT3 signaling by binding directly to STAT3. Significance: Galiellalactone is a promising direct STAT3 inhibitor for treatment of castration-resistant prostate cancer.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Galiellalactone Is a Direct Inhibitor of the Transcription Factor STAT3 in Prostate Cancer Cells

Don‐Doncow

Escobar

Johansson

et al. 2014

Journal of Biological Chemistry

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“…Moreover, this agent induced growth inhibition of human prostate (DU145) tumor xenografts delivered at 3 mg/kg per day intra-peritoneally [94], a promising in vivo activity and effect.…”

Section: Inhibitors Targeting the Stat3 Dna-binding Domainmentioning

confidence: 98%

STAT-3 Inhibitors: State of the Art and New Horizons for Cancer Treatment

Lavecchia

Giovanni²,

Novellino³

2011

CMC

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The signal transducers and activators of transcription (STATs) include a class of cytoplasmic signaling proteins whose role in the regulation of cell growth and survival is mediated by phosphorylation of a critical tyrosine residue within the STAT protein. This occurs in response to cytokines and growth factors modulating the expression of specific target genes. In particular, phosphorylation induces STAT:STAT dimer formation between two monomers, via reciprocal phosphoTyr (pTyr)-SH2 domain interactions. To date, seven members of the STAT family, all with different roles, have been identified in mammals. After dimerization, phosphorylated STATs enter the nucleus and, working co-ordinately with other transcriptional co-activators and transcription factors, induce increased transcriptional initiation. In healthy human and animal cells, ligand-dependent activation of STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular STAT1, 3 and 5) are persistently tyrosine-phosphorylated or activated; abnormal levels of STAT3 activation have been observed in breast, ovarian, prostate, hematological and head and neck cancer cell lines. Thus, in this review, we examine the most important classes of agents designed to disrupt STAT3 signaling, with particular regard to STAT3 dimerization inhibitors, which could play a significant role in the future of cancer and adjuvant cancer therapies.

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“…Galiellalactone (Weidler et al, 2000;Hellsten et al, 2008), flavopiridol (Lee et al, 2006) and a class of platinum (IV) compounds including IS3295 (Turkson et al, 2005), CPA-1, CPA-7 and platinum (V) tetrachloride (Turkson et al, 2004b), and decoy oligodeoxynucleotides (Xi et al, 2005;Zhang et al, 2007;Gu et al, 2008;Sun et al, 2008;Zhang et al, 2010;Barton et al, 2004) were found to interfere with Stat3 binding to DNA as well as induce cell growth inhibition and apoptosis of human breast, lung and prostate cancer cells (Hellsten et al, 2008;Barton et al, 2004;Zhang et al, 2010;Zhang et al, 2007;Xi et al, 2005;Sun et al, 2008;Gu et al, 2008;Turkson et al, 2004b;Turkson et al, 2005;Lee et al, 2006). Some of these inhibitors have been tested in animal models and they appear to cause regression of xenograft tumors.…”

Section: Stat3 Transcription Factormentioning

confidence: 99%

Disruption of Protein–DNA Interactions: An Opportunity for Cancer Chemotherapy

Neher¹,

Huang²,

Zhang³

et al. 2011

DNA Repair and Human Health

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Galiellalactone is a novel therapeutic candidate against hormone‐refractory prostate cancer expressing activated Stat3

Abstract: Galiellalactone induced growth inhibition and apoptosis in androgen-insensitive PCa cells expressing p-Stat3. We suggest that galiellalactone is a potential anti-tumor lead against hormone-refractory PCa with constitutively active Stat3.

Cited by 74 publications

References 47 publications

Galiellalactone Is a Direct Inhibitor of the Transcription Factor STAT3 in Prostate Cancer Cells

Galiellalactone Is a Direct Inhibitor of the Transcription Factor STAT3 in Prostate Cancer Cells

STAT-3 Inhibitors: State of the Art and New Horizons for Cancer Treatment

Disruption of Protein–DNA Interactions: An Opportunity for Cancer Chemotherapy

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