Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth

Lung, Wen; Chang, Ning; Yu, Yingchun; Su, Yuting; Chen, Guan-Yu; Cheng, Wei‐Chung; Wu, Yang‐Chang; Li, Ching-Chia; Chang, Wei-Chun; Yang, Juan-Cheng

doi:10.1002/cam4.4536

Cited by 19 publications

(10 citation statements)

References 42 publications

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“…The CYP19A1 gene exhibits polymorphism and mutations, which can alter its expression or aromatase activity, consequently impacting the overaccumulation of estrogen and cancer progression . In a study by Ma et al, it was found that CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) is associated with GCa prognosis . Taxifolin partly exerts an antigastric cancer effect by inhibiting the AhR/CYP1A1 signaling pathway .…”

Section: Resultsmentioning

confidence: 99%

“…41 In a study by Ma et al, it was found that CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) is associated with GCa prognosis. 42 Taxifolin partly exerts an antigastric cancer effect by inhibiting the AhR/CYP1A1 signaling pathway. 43 The FNDC1 gene, located on human chromosome 6q25.3, acts as a G-protein signaling-independent activator and activates G-protein signaling by interacting with Gβγ subunits.…”

Section: Boll Has Been Identified As a Key Rbp Involved In The Growth...mentioning

confidence: 99%

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Molecular Mechanism of Circ_0088300–BOLL Interaction Regulating Mitochondrial Metabolic Reprogramming and Involved in Gastric Cancer Growth and Metastasis

Chu,

Fei,

2023

J. Proteome Res.

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This study aims to investigate the effect and molecular mechanism of the interaction between circRNA circ_0088300 and the RNA binding protein (RBP) BOLL on the growth and metastasis of gastric cancer. A prognostic risk model was established by screening differentially expressed RBP genes from the TCGA database, and BOLL was identified as a critical RBP. Gene Set Enrichment analysis (GSEA) showed that BOLL was associated with mitochondrial function. The upregulation fold change of circ_0088300 was the highest in the GSE93541 data set, and the RPISeq database confirmed its binding relationship with BOLL. In vitro experiments showed that BOLL regulates mitochondrial metabolism and cancer cell function and circ_0088300 upregulates the expression level of BOLL. In vivo experiments demonstrated that knocking down circ_0088300 can inhibit tumor growth and metastasis, whereas overexpression of BOLL can reverse this effect. In conclusion, we have reached a preliminary conclusion that upregulation of BOLL by circ_0088300 promotes gastric cancer growth and metastasis by promoting mitochondrial metabolic reprogramming.

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Section: Resultsmentioning

confidence: 99%

Section: Boll Has Been Identified As a Key Rbp Involved In The Growth...mentioning

confidence: 99%

Molecular Mechanism of Circ_0088300–BOLL Interaction Regulating Mitochondrial Metabolic Reprogramming and Involved in Gastric Cancer Growth and Metastasis

Chu,

Fei,

2023

J. Proteome Res.

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“…Phytochemicals including UA may exert powerful efficacy against a variety of malignancies, such as CRC, gastric cancer, breast cancer, prostate cancer, , and lung cancer, with fewer adverse reactions in comparison with the compounds of chemotherapy, which gives rise to broad utilization of phytochemicals as nutraceuticals for intervention in various cancers. However, the action mechanisms for most phytochemicals remain to be clarified, and UA is one of them in great need of exploration.…”

Section: Discussionmentioning

confidence: 99%

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Zhao

Tang

Qiu

et al. 2023

J. Agric. Food Chem.

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Overwhelming evidence points to an abnormally active Wnt/β-catenin signaling as a key player in colorectal cancer (CRC) pathogenesis. Ursolic acid (UA) is a pentacyclic triterpenoid that has been found in a broad variety of fruits, spices, and medicinal plants. UA has been shown to have potent bioactivity against a variety of cancers, including CRC, with the action mechanism obscure. Our study tried to learn more about the efficacy of UA on CRC and its functional mechanism amid the Wnt/β-catenin signaling cascade. We determined the efficacy of UA on CRC SW620 cells with respect to the proliferation, migration, clonality, apoptosis, cell cycle, and Wnt/β-catenin signaling cascade, with assessment of the effect of UA on normal colonic NCM460 cells. Also, the effects of UA on the tumor development, apoptosis, cell cycle, and Wnt/β-catenin signaling axis were evaluated after a subcutaneous SW620 xenograft tumor model was established in mice. In this work, we showed that UA drastically suppressed proliferation, migration, and clonality; induced apoptosis; and arrested the cell cycle at the G0/G1 phase of SW620 cells, without the influence on NCM460 cells, accompanied by weakened activity of the Wnt/β-catenin signaling pathway. Besides, UA markedly deterred the growth of the xenograft tumor, ameliorated pathological features, triggered apoptosis, and arrested the cell cycle in xenograft CRC tissue, by lessening the Wnt/β-catenin signaling cascade. Overall, UA may inhibit the malignant phenotype, induce apoptosis, and arrest the cell cycle of CRC, potentially by attenuating the Wnt/β-catenin signaling axis, providing insights into the mechanism for the potency of UA on CRC.

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“…Heat-clearing and detoxifying properties of traditional Chinese, including Hedyotis diffusa, Oldenlandia diffusa, Prunella vulgaris, Scutellaria barbata, and Ligustrum lucidum, have shown signi cant e cacy in the treatment of CRC. These herbal medicines have been reported to promote tumor cell apoptosis, reverse multidrug resistance, and inhibit tumor angiogenesis [37][38][39]. However, the speci c mechanisms and targets of these herbal medicines require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Ursolic acid inhibits the growth of colorectal cancer cells through regulating the PKN2/Akt/ERK pathway by targeting SNTB1

Wen

Liu

Lin

et al. 2023

Preprint

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Background Colorectal cancer (CRC) is one of the most highly malignant tumors. Ursolic acid (UA) has been identified to exerts anti-CRC effects through the regulation of multiple genes and signaling pathways. Syntrophin beta 1 (SNTB1) has been implicated to have the potential as a new prognostic factor and therapeutic target for CRC. We wondered whether UA exert anti-CRC effects by regulating SNTB1 expression. Methods and Results CCK8 assay and colony staining was conducted to determine the cell viability and colony formation of Human CRC cell line HCT116. Lentiviral infection was employed for SNTB1 knockdown and overexpression. Western blot analysis was performed to detect the protein expression. The result shown that UA significantly inhibited cell viability and downregulated SNTB1 expression while upregulating PKN2 expression. It also decreased the ratios of p-Akt/Akt and p-ERK/ERK. UA significantly promoted the decrease of cell viability and colony formation in HCT116 cells with SNTB1 knockdown, the upregulation of PKN2 protein expression, and the downregulation of the p-Akt/Akt and p-ERK/ERK ratios. On the other hand, UA significantly inhibited the increase of cell viability and colony formation in HCT116 cells with SNTB1 overexpression, the downregulation of PKN2 protein expression, and the upregulation of the p-Akt/Akt and p-ERK/ERK ratios. Conclusion Take together, UA inhibits CRC cell growth may through regulating the PKN2/Akt/ERK pathway by targeting SNTB1. This study enriches the mechanisms underlying the anticancer effects of UA in CRC and provides new evidence for UA as a potential anti-CRC agent.

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Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 19 publications

References 42 publications

Molecular Mechanism of Circ_0088300–BOLL Interaction Regulating Mitochondrial Metabolic Reprogramming and Involved in Gastric Cancer Growth and Metastasis

Molecular Mechanism of Circ_0088300–BOLL Interaction Regulating Mitochondrial Metabolic Reprogramming and Involved in Gastric Cancer Growth and Metastasis

Ursolic Acid Suppresses Colorectal Cancer by Down-Regulation of Wnt/β-Catenin Signaling Pathway Activity

Ursolic acid inhibits the growth of colorectal cancer cells through regulating the PKN2/Akt/ERK pathway by targeting SNTB1

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