A Comparative Study on Anti-Invasion, Antimigration, and Antiadhesion Effects of the Bioactive Carotenoids of Saffron on 4T1 Breast Cancer Cells Through Their Effects on Wnt/β-Catenin Pathway Genes

Arzi, Laleh; Riazi, Gholamhossein; Majid, Shahana; Hoshyar, Reyhane; Jafarzadeh, Nazli

doi:10.1089/dna.2018.4248

Cited by 38 publications

(18 citation statements)

References 38 publications

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“…In previous studies of triple-negative breast cancer (TNBC), crocin inhibited the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/β-catenin and increased the weight, survival rate, and volume of tumors in mice. Crocin reduced metastasis, invasion, and extracellular adhesion of TNBC cells in a dose-dependent manner, and its mechanism was related to the inhibition of the downstream factors FZD7, NEDD9, VIM, and VEGF-a [35,36].…”

Section: Introductionmentioning

confidence: 96%

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Wang

et al. 2020

Neural Plasticity

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At present, most of the drugs have little effect on the pathological process of rheumatoid arthritis (RA). Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease. Some studies have found that crocin, a kind of Chinese medicine, can effectively alleviate pain sensitization in pain model rats, but the mechanism is not clear. Emerging evidence indicates that crocin may inhibit the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/β-catenin and the Wnt signaling pathway is closely related to RA. Wnt5a belongs to the Wnt protein family and was previously thought to be involved only in nonclassical Wnt signaling pathways. Recent studies have shown that Wnt5a has both stimulatory and inhibitory effects on the classical Wnt signaling pathway, and so, Wnt5a has attracted increasing attention. This study demonstrated that crocin significantly increased the mechanical thresholds of adjuvant-induced arthritis (AIA) rats, suggesting that crocin can alleviate neuropathic pain. Crocin significantly decreased the levels of pain-related factors and glial activation. Foxy5, activator of Wnt5a, inhibited the above effects of crocin in AIA rats. In addition, intrathecal injection of a Wnt5a inhibitor significantly decreased hyperalgesia in AIA rats. This research shows that crocin may alleviate neuropathic pain in AIA rats by inhibiting the expression of pain-related molecules through the Wnt5a/β-catenin pathway, elucidating the mechanism by which crocin relieves neuropathic pain and provides a new way of thinking for the treatment of AIA pain.

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Section: Introductionmentioning

confidence: 96%

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Wang

et al. 2020

Neural Plasticity

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“…In recent years, the anti-tumor effects of this herb have been investigated by a considerable number of different research groups in different tumor entities, including lung, breast, and colon cancer [ 13 ]. These studies gave hints for the possible anti-metastatic effects of saffron crudes and its compounds by downregulating metastasis-associated genes such as MMP-2, -9 and Wnt pathway target genes including FZD7, NEDD9, VIM, and VEGF-α [ 19 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells

Güllü

Kobelt

Brim

et al. 2020

Cells

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The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron’s anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.

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“…With respect to FZD7, the vast majority of studies focused on breast cancer, in particular triple-negative breast cancer (TNBC), for TNBC was unresponsive to classical endocrine therapy. FZD7 was thus considered as one of the important therapeutic targets in TNBC and showed an improved therapeutic e cacy as well [26][27][28][29][30]. However, little is known about the role of FZD7 in PAAD to date.…”

Section: Discussionmentioning

confidence: 99%

Expression and Prognostic Impact of FZDs in Pancreatic Adenocarcinoma

Liu

Zhang

2020

Preprint

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Background: Despite the high number of researches on pancreatic adenocarcinoma (PAAD) over past decades, little progress had been made due to lack of effective treatment regimens. we aimed to investigate the expression level, mutation, and clinical significance of the Frizzled (FZD) family in PAAD so as to establish a sufficient scientific evidence for clinical decisions and risk management.Methods: PAAD samples were extracted from The Cancer Genome Atlas (TCGA). Oncomine, Gene expression profiling interactive analysis (GEPIA), Human Protein Atlas (HPA), Kaplan-Meier Plotter, cBioPortal, LinkedOmics, DAVID database, and R software (x64 3.6.2) were used to comprehensively analyze the roles of FZDs. p-value below to 0.05 was considered as significant difference.Results: In total, 179 PAAD tissues and 171 paracancerous tissues were included. The expression levels of FZD1, 2, 6, 7, and 8 were higher in PAAD tissues than those in normal pancreatic tissue. The higher the expression levels of FZD2 and FZD7, the higher the clinical stage. PAAD patients with high expression of FZD6 had shorter overall survival (OS) than those with low expression, indicating that FZD6 could be a potential prognostic and predictive marker in PAAD. PAAD patients with high expression of FZD8 had shorter recurrence free survival (RFS) than those with low expression, indicating that FZD8 could be a potential therapeutic target in PAAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that FZDs played a critical role in the Wnt signaling pathway, which was further confirmation that FZDs were transmembrane receptors of Wnt signaling pathway. Conclusions: Our results strongly indicated a crucial role of the FZD family in PAAD. FZD3, 4, 5, 6, and 9 could be potential prognostic and predictive markers, and FZD4 and 8 might function as potential therapeutic targets in PAAD.

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A Comparative Study on Anti-Invasion, Antimigration, and Antiadhesion Effects of the Bioactive Carotenoids of Saffron on 4T1 Breast Cancer Cells Through Their Effects on Wnt/β-Catenin Pathway Genes

Cited by 38 publications

References 38 publications

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells

Expression and Prognostic Impact of FZDs in Pancreatic Adenocarcinoma

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