The curcumin analogue hydrazinocurcumin exhibits potent suppressive activity on carcinogenicity of breast cancer cells via STAT3 inhibition

Wang, Xiaofei; Zhang, Yan; Zhang, Xiwen; Tian, Wen; Feng, Wenli; Chen, Tingmei

doi:10.3892/ijo.2011.1298

Cited by 41 publications

(28 citation statements)

References 44 publications

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“…In our previous study, we demonstrated that HC was an effective inhibitor of STAT3 phosphorylation. It could down-regulate an array of STAT3 downstream targets that contributed to the suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion as well as induction cell apoptosis in vitro[13]. Therefore, in this study, HC was employed to suppress STAT3 activity, and re-educate TAMs to change from M2 to M1.…”

Section: Introductionmentioning

confidence: 99%

Hydrazinocurcumin Encapsuled Nanoparticles “Re-Educate” Tumor-Associated Macrophages and Exhibit Anti-Tumor Effects on Breast Cancer Following STAT3 Suppression

et al. 2013

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Tumor-associated macrophages (TAMs) are essential cellular components within tumor microenvironment (TME). TAMs are educated by TME to transform to M2 polarized population, showing a M2-like phenotype, IL-10high, IL-12low, TGF-βhigh. STAT3 signaling triggers crosstalk between tumor cells and TAMs, and is crucial for the regulation of malignant progression. In our study, legumain-targeting liposomal nanoparticles (NPs) encapsulating HC were employed to suppress STAT3 activity and “re-educate” TAMs, and to investigate the effects of suppression of tumor progression in vivo. The results showed that TAMs treated by HC encapsuled NPs could switch to M1-like phenotype, IL-10low, IL-12high, TGF-βlow, and the “re-educated” macrophages (M1-like macrophages) considerably demonstrated opposite effect of M2-like macrophages, especially the induction of 4T1 cells migration and invasion in vitro, and suppression of tumor growth, angiogenesis and metastasis in vivo. These data indicated that inhibition of STAT3 activity of TAMs by HC-NPs was able to reverse their phenotype and could regulate their crosstalk between tumor cells and TAMs in order to suppress tumor progression.

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Section: Introductionmentioning

confidence: 99%

Hydrazinocurcumin Encapsuled Nanoparticles “Re-Educate” Tumor-Associated Macrophages and Exhibit Anti-Tumor Effects on Breast Cancer Following STAT3 Suppression

et al. 2013

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“…During efficacy testing of hydrazinocurcumin (HC), a synthetic curcumin analogue, inhibition of STAT3 phosphorylation in BC cell lines (MDA‐MB‐231, MCF‐7) decreased the expression of c‐Myc, Bcl‐xL, Bcl‐2, Mcl‐1, cyclin D1/D2, VEGF, MMP‐2 and MMP‐9 among others . Another compound benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetable, inhibited Leptin stimulated migration and invasion of MDA‐MB‐231 and MCF‐7 human BC cells .…”

Section: Constitutive Activation Of Stat3 and Regulation Of Gene Exprmentioning

confidence: 99%

“…85 During efficacy testing of hydrazinocurcumin (HC), a synthetic curcumin analogue, inhibition of STAT3 phosphorylation in BC cell lines (MDA-MB-231, MCF-7) decreased the expression of c-Myc, Bcl-xL, Bcl-2, Mcl-1, cyclin D1/D2, VEGF, MMP-2 and MMP-9 among others. 86,87 Another compound benzyl isothiocyanate (BITC), a constituent of edible cruciferous vegetable, inhibited Leptin stimulated migration and invasion of MDA-MB-231 and MCF-7 human BC cells. 88 BITC treatment suppressed leptin induced STAT3 phosphorylation and Cyclin D1 transactivation by inhibiting STAT3 recruitment to the Cyclin D1 promoter as detected in chromatin immunoprecipitation (ChIP) analysis.…”

Section: Constitutive Activation Of Stat3 and Regulation Of Gene Exprmentioning

confidence: 99%

Constitutive activation of STAT3 in breast cancer cells: A review

Banerjee

Resat

2015

Intl Journal of Cancer

509

394

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Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in numerous cancer types, including more than 40% of breast cancers. In contrast to tight regulation of STAT3 as a latent transcription factor in normal cells, its signaling in breast cancer oncogenesis is multifaceted. Signaling through the IL6/JAK/STAT3 pathway initiated by the binding of IL6 family of cytokines (i.e., IL-6, IL-11) to their receptors have been implicated in breast cancer development. Receptors with intrinsic kinase activity such as EGFR and VEGFR directly or indirectly induce STAT3 activation in various breast cancer types. Aberrant STAT3 signaling promotes breast tumor progression through deregulation of the expression of downstream target genes which control proliferation (Bcl-2, Bcl-xL, Survivin, Cyclin D1, c-Myc, Mcl-1), angiogenesis (Hif1α, VEGF), and epithelial-mesenchymal transition (Vimentin, TWIST, MMP-9, MMP-7). These multiple modes of STAT3 regulation therefore make it a central linking point for a multitude of signaling processes. Extensive efforts to target STAT3 activation in breast cancer had no remarkable success in the past because the highly-interconnected nature of STAT3 signaling introduces lack of selectivity in pathway identification for STAT3 targeted molecular therapies or because its role in tumorigenesis may not be as critical as it was thought. This review provides a full spectrum of STAT3’s involvement in breast cancer by consolidating the knowledge about its role in breast cancer development at multiple levels: its differential regulation by different receptor signaling pathways, its downstream target genes, and modification of its transcriptional activity by its co-regulatory transcription factors.

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“…A study demonstrated that in breast cancer cells, phosphorylated STAT3 up-regulates the EMT associated protein, TWIST (Lo et al, 2007). Further, several studies have demonstrated that STAT3 up-regulates MMP2, MMP7 and MMP9 in breast cancer cell lines Yuan et al, 2008;Wang et al, 2012), proteins that are heavily associated with EMT. Additionally, through regulation of EMT/stemness, STAT3 may also play a role in regulating drug resistance, as it was shown that in human breast cancer, feedback activation of the IL6-STAT3 loop induced EMT and cancer stem cell features, leading to resistance to PI3K inhibitors (Yang et al, 2014).…”

Section: Phosphoinositide 3-kinase (Pi3k)/ Akt/mechanistic Target Of mentioning

confidence: 99%

Cellular Plasticity in Breast Cancer Progression and Therapy

Kong

Hughes

Ford

2020

Front. Mol. Biosci.

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With the exception of non-melanoma skin cancer, breast cancer is the most frequently diagnosed malignant disease among women, with the majority of mortality being attributable to metastatic disease. Thus, even with improved early screening and more targeted treatments which may enable better detection and control of early disease progression, metastatic disease remains a significant problem. While targeted therapies exist for breast cancer patients with particular subtypes of the disease (Her2+ and ER/PR+), even in these subtypes the therapies are often not efficacious once the patient's tumor metastasizes. Increases in stemness or epithelial-to-mesenchymal transition (EMT) in primary breast cancer cells lead to enhanced plasticity, enabling tumor progression, therapeutic resistance, and distant metastatic spread. Numerous signaling pathways, including MAPK, PI3K, STAT3, Wnt, Hedgehog, and Notch, amongst others, play a critical role in maintaining cell plasticity in breast cancer. Understanding the cellular and molecular mechanisms that regulate breast cancer cell plasticity is essential for understanding the biology of breast cancer progression and for developing novel and more effective therapeutic strategies for targeting metastatic disease. In this review we summarize relevant literature on mechanisms associated with breast cancer plasticity, tumor progression, and drug resistance.

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The curcumin analogue hydrazinocurcumin exhibits potent suppressive activity on carcinogenicity of breast cancer cells via STAT3 inhibition

Cited by 41 publications

References 44 publications

Hydrazinocurcumin Encapsuled Nanoparticles “Re-Educate” Tumor-Associated Macrophages and Exhibit Anti-Tumor Effects on Breast Cancer Following STAT3 Suppression

Hydrazinocurcumin Encapsuled Nanoparticles “Re-Educate” Tumor-Associated Macrophages and Exhibit Anti-Tumor Effects on Breast Cancer Following STAT3 Suppression

Constitutive activation of STAT3 in breast cancer cells: A review

Cellular Plasticity in Breast Cancer Progression and Therapy

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