Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

Leow, Pay-Chin; Bahety, Priti; Boon, Choon Pei; Lee, Chong Yew; Tan, Kheng Lin; Yang, Taowei; Ee, Pui Lai Rachel

doi:10.1016/j.ejmech.2013.10.073

Cited by 49 publications

(27 citation statements)

References 46 publications

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“…However, a recent report showed that modification of the basic flavone core improves the selectivity and potency of flavones in Wnt/β-catenin modulation [37]. Similar studies have been performed with other natural substances and also synthetic compounds [38,39]. Moreover, we can observe once again differences of derricin and derricidin effects concerning cell line specificity.…”

Section: Discussionsupporting

confidence: 81%

Derricin and Derricidin Inhibit Wnt/β-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro

et al. 2015

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Overactivation of the Wnt/β-catenin pathway in adult tissues has been implicated in many diseases, such as colorectal cancer. Finding chemical substances that can prevent this phenomenon is an emerging problem. Recently, several natural compounds have been described as Wnt/β-catenin inhibitors and might be promising agents for the control of carcinogenesis. Here, we describe two natural substances, derricin and derricidin, belonging to the chalcone subclass, that show potent transcriptional inhibition of the Wnt/β-catenin pathway. Both chalcones are able to affect the cell distribution of β-catenin, and inhibit Wnt-specific reporter activity in HCT116 cells and in Xenopus embryos. Derricin and derricidin also strongly inhibited canonical Wnt activity in vitro, and rescued the Wnt-induced double axis phenotype in Xenopus embryos. As a consequence of Wnt/β-catenin inhibition, derricin and derricidin treatments reduce cell viability and lead to cell cycle arrest in colorectal cancer cell lines. Taken together, our results strongly support these chalcones as novel negative modulators of the Wnt/β-catenin pathway and colon cancer cell growth in vitro.

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Section: Discussionsupporting

confidence: 81%

Derricin and Derricidin Inhibit Wnt/β-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro

et al. 2015

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“…Among these compounds 3,5-bis (substituted cinnamylidene)-N-alkyl-4-peperidone is the most active against the administration of the prophylactic treatment for four weeks before the induction of cancer by 1,2-dimethylhydrazine 146 . Leow et al 147 synthesized a total of five series consisting of 43 CUR analogs and screened in HEK293T cells for inhibition of β-catenin transcriptional activity. These analogs were more potent than parent CUR as effective wnt inhibitors and anti-invasive agents in human osteosarcoma.…”

Section: Biological Activities Of Various Curcuminoid Formulationsmentioning

confidence: 99%

Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review

Amalraj¹,

Pius

Gopi

et al. 2017

Journal of Traditional and Complementary Medicine

730

413

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In recent years, several drugs have been developed deriving from traditional products and current drug research is actively investigating the possible therapeutic roles of many Ayruvedic and Traditional Indian medicinal therapies. Among those being investigated is Turmeric. Its most important active ingredient is curcuminoids. Curcuminoids are phenolic compounds commonly used as a spice, pigment and additive also utilized as a therapeutic agent used in several foods. Comprehensive research over the last century has revealed several important functions of curcuminoids. Various preclinical cell culture and animals studies suggest that curcuminoids have extensive biological activity as an antioxidant, neuroprotective, antitumor, anti-inflammatory, anti-acidogenic, radioprotective and arthritis. Different clinical trials also suggest a potential therapeutic role for curcuminoids in numerous chronic diseases such as colon cancer, lung cancer, breast cancer, inflammatory bowel diseases. The aim of this review is to summarize the chemistry, analog, metal complex, formulations of curcuminoids and their biological activities.

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“…When GSK-3β is inactivated, β-catenin is released from the destruction complex and allowed to accumulate in the cytoplasm and migrate to the nucleus. In the nucleus, accumulated β-catenin interacting with the TCF/LEF family of DNA-bound transcription factors activates downstream target genes, mainly oncogenes, cell cycle regulators, VEGF and matrix degrading enzymes, affecting the occurrence and development of cancers (Leow et al, 2014).…”

Section: Fnc Inhibition Of Non-hodgkin Lymphoma Cell Invasion Via Thementioning

confidence: 99%

FNC, a Novel Nucleoside Analogue, Blocks Invasion of Aggressive Non-Hodgkin Lymphoma Cell Lines Via Inhibition of the Wnt/β-Catenin Signaling Pathway

Zhang

Wang²,

Ding³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2' -β-fluoro -4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with IC 50 values of 0.2μM and 0.097μM, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of β-catenin, the glycogen synthase kinase-3 beta (GSK-3β), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, β-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-3β and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/β-catenin signaling pathway.

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Functionalized curcumin analogs as potent modulators of the Wnt/β-catenin signaling pathway

Cited by 49 publications

References 46 publications

Derricin and Derricidin Inhibit Wnt/β-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro

Derricin and Derricidin Inhibit Wnt/β-Catenin Signaling and Suppress Colon Cancer Cell Growth In Vitro

Biological activities of curcuminoids, other biomolecules from turmeric and their derivatives – A review

FNC, a Novel Nucleoside Analogue, Blocks Invasion of Aggressive Non-Hodgkin Lymphoma Cell Lines Via Inhibition of the Wnt/β-Catenin Signaling Pathway

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