Curcumin inhibits invasion and metastasis of human hepatoma cells through Bclaf1-mediated Wnt/β-catenin signalling

Zhao, Zhongwei; Su, Jielin; Zhao, Jiaqi; Chen, Jiaxin; Cui, Xinmu; Sun, Manqing; Zhang, Xuewu

doi:10.1080/09540105.2022.2113864

Cited by 7 publications

(2 citation statements)

References 25 publications

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“…Recent studies showed that curcumin exerted anti-inflammatory, pro-, and antioxidant [ 4 ], anticancer [ 5 ], and antibacterial [ 6 ] activity. Curcumin increases the expression of various genes and is involved in several signaling pathways, e.g., NF-κB [ 7 ], MAPK [ 8 ], JAK/STAT [ 9 ], WNT/β-catenin [ 10 ], Hippo [ 11 ], NOTCH [ 12 ], and Akt/mTOR [ 13 ] pathways. Moreover, curcumin can be used as a photosensitizer for anticancer and antibacterial photodynamic therapy (PDT) [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure–Activity Evaluation, and Biological Activity

Łażewski

Kucińska

Potapskiy

et al. 2023

IJMS

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Curcumin has been modified in various ways to broaden its application in medicine and address its limitations. In this study, we present a series of curcumin-based derivatives obtained by replacing the hydroxy groups in the feruloyl moiety with polyethylene glycol (PEG) chains and the addition of the BF2 moiety to the carbonyl groups. Tested compounds were screened for their cytotoxic activity toward two bladder cancer cell lines, 5637 and SCaBER, and a noncancerous cell line derived from lung fibroblasts (MRC-5). Cell viability was analyzed under normoxic and hypoxic conditions (1% oxygen). Structure–activity relationships (SARs) are discussed, and curcumin derivatives equipped within feruloyl moieties with 3-methoxy and 4-{2-[2-(2-methoxyethoxy)ethoxy]ethoxy} substituents (5) were selected for further analysis. Compound 5 did not affect the viability of MRC-5 cells and exerted a stronger cytotoxic effect under hypoxic conditions. However, the flow cytometry studies showed that PEGylation did not improve cellular uptake. Another observation was that the lack of serum proteins limits the intracellular uptake of curcumin derivative 5. The preliminary mechanism of action studies indicated that compound 5 under hypoxic conditions induced G2/M arrest in a dose-dependent manner and increased the expression of stress-related proteins such as p21/CIP1, phosphorylated HSP27, ADAMTS-1, and phosphorylated JNK. In summary, the results of the studies indicated that PEGylated curcumin is a more potent compound against bladder cancer cell lines than the parent compound, and derivative 5 is worthy of further investigation to clarify its mechanism of anticancer action under hypoxic conditions.

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Section: Introductionmentioning

confidence: 99%

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure–Activity Evaluation, and Biological Activity

Łażewski

Kucińska

Potapskiy

et al. 2023

IJMS

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“…Numerous studies have been conducted on the anti-tumor activities of both 6-shogaol and curcumin; for example, 6-shogaol can signi cantly inhibit the progression of a variety of malignant tumours (Lung and breast cancer) by reducing the release of CC-chemokine ligand (CCL-2) from tumour-associated dendritic cells [9]; 6-shogaol inhibits cell autophagy by inducing G2/M phase cell cycle block and by targeting Notch signalling pathway to inhibit cellular autophagy exacerbating apoptosis, thereby inhibiting breast cancer progression [10]; it can also inhibit apoptosis in hepatocellular carcinoma cells by targeting p53, thereby effectively enhancing the sensitivity of hepatocellular carcinoma cells to TRAIL-induced apoptosis [11]. Additionally, curcumin can inhibit tumor interstitial cell death by inhibiting the IL-6/ERK/NF-κB pathway to inhibit tumor mesenchymal crosstalk and pancreatic cancer metastasis and also inhibit HCC as well as improve drug resistance [12]; curcumin inhibits human hepatocellular carcinoma cell invasion and metastasis through Bclaf1-mediated Wnt/βcatenin signalling [13]; curcumin inhibits PI3K/AKT/GSK-3β pathway activation and triggered apoptosis in HCC mitochondria [14]. Many molecular pathways have been implicated in HCC carcinogenesis, including TERT promoter mutations, Wnt/β-linked protein, P53, Akt/mTOR, vascular endothelial growth factor receptor (VEGFR) and endothelial growth factor receptor (EGFR)/RAS/MAPK pathways [15].…”

Section: Introductionmentioning

confidence: 99%

Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network- based pharmacological and cellular assay

Jin,

Jiao,

Lian

et al. 2023

Preprint

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Background Hepatocellular carcinoma currently has the third highest mortality rate in the world. Patients with hepatocellular carcinoma are on the rise and at a younger age, but research into the pharmacological effects of cancer is mostly single-component, and natural plant products can have additive or synergistic effects that can better amplify the effects of intervention in cancer. Aim To evaluate the synergistic therapeutic effects of 6-shogaol and curcumin against hepatocellular carcinoma line HepG2 cells. Methods In this study, a network pharmacology approach was used to predict and validate the mol ecular targets and pathways of the hepatocellular carcinoma (HCC) of 6-shogaol and curcumin in combination and to investigate their mechanism of action. The results were also validated by cellular assays.HepG2 cells were treated with 6-shogaol and curcumin as well as the combination of the two. The combination index (CI) of 6-shogaol and curcumin in HepG2 cells was calculated using Compusyn software according to the Chou-Talalay equation.The synergistic anti-cancer effect was next investigated by MTT assay, apoptosis assay and cell cycle assay. The combined anti-hepatocellular carcinoma effect of the Ras-mediated PI3K/AKT and MAPK signalling pathways was analysed using protein blotting assays. Results A network pharmacology-based screening identified 72 core targets of 6-curcumin and curcumin in hepatocellular carcinoma, and predicted that the main signalling pathway is the Ras signalling pathway. The anti-cancer effects of 6-shogaol and curcumin were validated in cell-based assays and the optimal synergistic concentrations of 5 µmoL/L for 6-shogaol and 30 µmoL/L for curcumin were determined. 6-shogaol and curcumin synergistically blocked the cell cycle in the G2/M phase and promoted apoptosis. Immunoblot analysis confirmed for the first time the combined action of both in down-regulating the Ras-mediated PI3K/AKT and MAPK signaling pathways. In addition, 6-shogaol and curcumin acting together down-regulated Cyclin-B, CDK-1, Bcl-2, and up-regulated BAX. Conclusion 6-shogaol and curcumin act synergistically to alter the morphology of hepatocellular carcinoma cells, block the cell cycle in the G2/M phase, inhibit proliferation and division, and effectively promote late apoptosis. The combined action of these two components provides a theoretical basis for the further development of novel anti-liver cancer products.

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Exploring the Interaction of Lipid Bilayers with Curcumin–Laponite Nanoparticles: Implications for Drug Delivery and Therapeutic Applications

Pawar,

Peña‐Figueroa,

Verde‐Sesto

et al. 2024

Small

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Curcumin, the active compound in turmeric, is renowned for its anti‐inflammatory, antioxidant, and antimicrobial properties, making it beneficial for treating conditions like arthritis, neurodegenerative diseases, and various cancers. Despite its promising therapeutic potential, curcumin's poor bioavailability—due to its rapid metabolism and low solubility—limits its clinical efficacy. To address this, recent research has focused on enhancing curcumin delivery using nanoparticles, liposomes, and novel nanomaterials. Among these, laponite, a synthetic nanoclay, has shown promise in improving curcumin delivery due to its unique properties, including large surface area, dual charge, and stability in solution. This study explores the use of curcumin–laponite nanoparticles as carrier vehicles for controlled delivery to in vitro model membranes. Utilizing advanced techniques such as neutron reflectometry, atomic force microscopy, quartz crystal microbalance with dissipation, and infrared spectroscopy, the interaction between curcumin–laponite nanoparticles and solid‐supported lipid bilayers is monitored, revealing enhanced stability and controlled release of curcumin across the membrane. These findings pave the way for the development of curcumin‐based therapies targeting cardiovascular, neurological, and oncological diseases, leveraging the synergistic effects of curcumin's biological activity and laponite's delivery capabilities.

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Curcumin inhibits invasion and metastasis of human hepatoma cells through Bclaf1-mediated Wnt/β-catenin signalling

Cited by 7 publications

References 25 publications

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure–Activity Evaluation, and Biological Activity

Enhanced Cytotoxic Activity of PEGylated Curcumin Derivatives: Synthesis, Structure–Activity Evaluation, and Biological Activity

Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network- based pharmacological and cellular assay

Exploring the Interaction of Lipid Bilayers with Curcumin–Laponite Nanoparticles: Implications for Drug Delivery and Therapeutic Applications

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