Piceatannol Prevents Colon Cancer Progression via Dual‐Targeting to M2‐Polarized Tumor‐Associated Macrophages and the TGF‐β1 Positive Feedback Signaling Pathway

Chiou, Yi‐Shiou; Lan, Yi‐Ming; Lee, Pei‐Sheng; Lin, Qianyu; Nagabhushanam, Kalyanam; Ho, Chi‐Tang; Pan, Min‐Hsiung

doi:10.1002/mnfr.202200248

Cited by 11 publications

(4 citation statements)

References 31 publications

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“… 190 Piceatannol (PIC), another natural arginase inhibitor, can effectively inhibit TGF-β1 /TGF-β receptor type 1 (TGF-βR1) signaling pathway, limit M2-type macrophage polarization to regulate TME and inhibit CRC progression and metastasis. 191 These results suggest that ARG is a potential target for tumor metabolism. Arginase inhibitors have been developed and experimentally evaluated in various tumors.…”

Section: Arginine (Arg)mentioning

confidence: 89%

Amino acid metabolism in health and disease

Ling,

Jiang,

et al. 2023

Sig Transduct Target Ther

104

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Amino acids are the building blocks of protein synthesis. They are structural elements and energy sources of cells necessary for normal cell growth, differentiation and function. Amino acid metabolism disorders have been linked with a number of pathological conditions, including metabolic diseases, cardiovascular diseases, immune diseases, and cancer. In the case of tumors, alterations in amino acid metabolism can be used not only as clinical indicators of cancer progression but also as therapeutic strategies. Since the growth and development of tumors depend on the intake of foreign amino acids, more and more studies have targeted the metabolism of tumor-related amino acids to selectively kill tumor cells. Furthermore, immune-related studies have confirmed that amino acid metabolism regulates the function of effector T cells and regulatory T cells, affecting the function of immune cells. Therefore, studying amino acid metabolism associated with disease and identifying targets in amino acid metabolic pathways may be helpful for disease treatment. This article mainly focuses on the research of amino acid metabolism in tumor-oriented diseases, and reviews the research and clinical research progress of metabolic diseases, cardiovascular diseases and immune-related diseases related to amino acid metabolism, in order to provide theoretical basis for targeted therapy of amino acid metabolism.

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Section: Arginine (Arg)mentioning

confidence: 89%

Amino acid metabolism in health and disease

Ling,

Jiang,

et al. 2023

Sig Transduct Target Ther

104

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“…Overall, EIF5A2 is the key gene that simultaneously regulates the interaction between EMT and stemness. Meanwhile, there are many common signaling pathways between EMT and stemness, such as PI3K/Akt, Wnt/β-catenin and TGF-β [ 33 , 34 , 35 ]. Because of this, through KEGG and GSVA enrichment analyses, we realized that EIF5A2/PI3k/Akt was the key signaling pathway regulating HCC EMT and stemness.…”

Section: Discussionmentioning

confidence: 99%

Genistein Restricts the Epithelial Mesenchymal Transformation (EMT) and Stemness of Hepatocellular Carcinoma via Upregulating miR-1275 to Inhibit the EIF5A2/PI3K/Akt Pathway

Yang

Jiang

Kong

et al. 2022

Biology

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Purpose: Genistein is a natural phytoestrogen with various antitumor effects. In recent years, some microRNAs (miRNA) in cancer cells have been reported to be regulated by genistein. Our study focused on exploring the mechanisms of miRNA upregulation to inhibit the epithelial mesenchymal transformation (EMT) and stemness of hepatocellular carcinoma (HCC). Patients and Methods: MiR-1275 was discovered by the transcriptome sequencing of miRNA expression profiles in HepG2 cells treated with genistein or DMSO as a control. Then, we performed series functional experiments in vitro and vivo to explore the relationship between genistein and miR-1275 in HCC. The target gene (Eukaryotic initiation factor 5A2, EIF5A2) of miR-1275 was predicted by databases and finally determined by a dual luciferase reporter assay. The downstream signaling pathway of EIF5A2 was assessed by bioinformatics analysis and Western blot. Results: the inhibition of genistein on the viability of HCC cells was enhanced by the increase in treatment time and dose, but it had no obvious inhibitory effect on normal hepatocytes (QSG-7701). Through qRT-PCR and transcriptome sequencing, we discovered that miR-1275 was lowly expressed in HCC, and it can be raised by genistein. The overall survival (OS) and recurrence-free survival (RFS) of HCC patients with lowly expressed miR-1275 were lower than those of those with high expression levels. In vitro and vivo experiments exhibited that genistein and the overexpression of miR-1275 can both significantly suppress the proliferation, migration, invasion, metastasis, EMT and stemness of HCC. Moreover, the inhibition can be further enhanced when miR-1275 mimic and genistein exist together. Finally, we demonstrated that miR-1275 can inhibit the epithelial mesenchymal transformation (EMT) and stemness of HCC via inhibiting the EIF5A2/PI3K/Akt pathway. Conclusion: Our findings proved that genistein can inhibit the EIF5A2/PI3K/Akt pathway by upregulating miR-1275 so as to attenuate the EMT and stemness of HCC cells to restrict their progression and metastasis.

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“…A ketogenic diet restrains colon tumors via inducing intratumor oxidative stress through downregulation of MMP9 expression, and facilitating the polarization of TAM towards an M1-like proinflammatory phenotype[ 112 ]. By re-educating TAMs in CRC, piceatannol is an effective TGF-β1/TGF-Βr1 pathway inhibitor and TME modulator that inhibits tumor progression and metastasis[ 113 ]. Licorne-mediated immunogenic photodynamic therapy synergizes with myeloid-derived suppressor cell (MDSC)-targeting immunotherapy[ 114 ], Bte-Pd-Au-R-combined radiophotothermal therapy[ 115 ], as well as combination of foretinib and anti-PD-1 antibody immunotherapy[ 116 ] significantly inhibited tumor growth via decreasing tumor infiltration or the percentage of M2-like TAMs.…”

Section: Tams and Targeted Therapies Of Digestive System Malignant Tu...mentioning

confidence: 99%

Role of tumor-associated macrophages in common digestive system malignant tumors

Shen¹,

Chen²,

Li³

et al. 2023

World J Gastrointest Oncol

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Many digestive system malignant tumors are characterized by high incidence and mortality rate. Increasing evidence has revealed that the tumor microenvironment (TME) is involved in cancer initiation and tumor progression. Tumor-associated macrophages (TAMs) are a predominant constituent of the TME, and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer. TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype. The latter especially are crucial drivers of tumor invasion, growth, angiogenesis, metastasis, immunosuppression, and resistance to therapy. TAMs are of importance in the occurrence, development, diagnosis, prognosis, and treatment of common digestive system malignant tumors. In this review, we summarize the role of TAMs in common digestive system malignant tumors, including esophageal, gastric, colorectal, pancreatic and liver cancers. How TAMs promote the development of tumors, and how they act as potential therapeutic targets and their clinical applications are also described.

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Piceatannol Prevents Colon Cancer Progression via Dual‐Targeting to M2‐Polarized Tumor‐Associated Macrophages and the TGF‐β1 Positive Feedback Signaling Pathway

Cited by 11 publications

References 31 publications

Amino acid metabolism in health and disease

Amino acid metabolism in health and disease

Genistein Restricts the Epithelial Mesenchymal Transformation (EMT) and Stemness of Hepatocellular Carcinoma via Upregulating miR-1275 to Inhibit the EIF5A2/PI3K/Akt Pathway

Role of tumor-associated macrophages in common digestive system malignant tumors

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