Andrographolide suppresses breast cancer progression by modulating tumor‐associated macrophage polarization through the Wnt/<i>β</i>‐catenin pathway

Liu, Lin; Yang, Lili; Yang, Shi Yu; Wang, Run‐Qing; Gao, Hui; Lin, Zhuying; Zhao, Yiyi; Tang, Weiwei; Han, Rui; Wang, Wen‐Ju; Liu, Ping; Hou, Zongliu; Meng, Mingyao; Liao, Lili

doi:10.1002/ptr.7578

Cited by 14 publications

(5 citation statements)

References 47 publications

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“…Many herbal components have been shown to play a role in TAM polarization, such as andrographolide [54] and curcumin [55]; however, not much is known regarding the effects of SAA on TAMs. In our study, we hypothesized that SAA could inhibit M2-like TAM polarization from a pro-tumor phenotype to an anti-tumor phenotype after treating macrophages with a TNBC-cell-conditional medium.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer

Tang,

Jiang,

et al. 2024

Molecules

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Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, with a high degree of malignancy and poor prognosis. Tumor-associated macrophages (TAMs) have been identified as significant contributors to the growth and metastasis of TNBC through the secretion of various growth factors and chemokines. Salvianolic acid A (SAA) has been shown to have anti-cancer activities. However, the potential activity of SAA on re-polarized TAMs remains unclear. As there is a correlation between the TAMs and TNBC, this study investigates the effect of SAA on TAMs in the TNBC microenvironment. For that purpose, M2 TAM polarization was induced by two kinds of TNBC-conditioned medium (TNBC-TCM) in the absence or presence of SAA. The gene and protein expression of TAM markers were analyzed by qPCR, FCM, IF, ELISA, and Western blot. The protein expression levels of ERK and p-ERK in M2-like TAMs were analyzed by Western blot. The migration and invasion properties of M2-like TAMs were analyzed by Transwell assays. Here, we demonstrated that SAA increased the expression levels of CD86, IL-1β, and iNOS in M2-like TAMs and, conversely, decreased the expression levels of Arg-1 and CD206. Moreover, SAA inhibited the migration and invasion properties of M2-like TAMs effectively and decreased the protein expression of TGF-β1 and p-ERK in a concentration-dependent manner, as well as TGF-β1 gene expression and secretion. Our current findings for the first time demonstrated that SAA inhibits macrophage polarization to M2-like TAMs by inhibiting the ERK pathway and promotes M2-like TAM re-polarization to the M1 TAMs, which may exert its anti-tumor effect by regulating M1/M2 TAM polarization. These findings highlight SAA as a potential regulator of M2 TAMs and the possibility of utilizing SAA to reprogram M2 TAMs offers promising insights for the clinical management of TNBC.

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Section: Discussionmentioning

confidence: 99%

The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer

Tang,

Jiang,

et al. 2024

Molecules

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“…Accumulating evidence suggests that aberrant glycoproteins of tumour cells are involved in the regulation of signaling pathways related to cell growth [ 34 ], proliferation and adhesion [ 35 , 36 ]. Nuclear translocation of β-catenin in the Wnt/β-catenin signaling pathway increases the expression levels of c-Myc and MMPs, thereby accelerating cancer progression [ 37 , 38 ]. β-catenin protein prevents hepatocellular carcinoma cell apoptosis by triggering EMT and up-regulating MMPs levels and enhances the migration ability of hepatocellular carcinoma cells [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/β-catenin signaling pathways in clear cell renal cell carcinoma

Jian,

Zhang,

Gong

et al. 2023

Cancer Cell Int

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Background CD56 has been observed in malignant tumours exhibiting neuronal or neuroendocrine differentiation, such as breast cancer, small-cell lung cancer, and neuroblastoma. Abnormal glycosylation modifications are thought to play a role in regulating tumour cell proliferation, migration, and invasion. Nevertheless, the exact roles and molecular mechanisms of CD56 and polysialylated CD56 (PSA-CD56) in the development and progression of clear cell renal cell carcinoma (ccRCC) remain elusive. Here we unveil the biological significance of CD56 and PSA-CD56 in ccRCC. Methods In this study, we employed various techniques, including immunohistochemistry (IHC), RT-qPCR, and western blot, to examine the mRNA and protein expression levels in both human ccRCC tissue and cell lines. Lentivirus infection and CRISPR/Cas9 system were utilized to generate overexpression and knockout cell lines of CD56. Additionally, we conducted several functional assays, such as CCK-8, colony formation, cell scratch, and transwell assays to evaluate cell growth, proliferation, migration, and invasion. Furthermore, we established a xenograft tumor model to investigate the role of CD56 in ccRCC in vivo. To gain further insights into the molecular mechanisms associated with CD56, we employed the Hedgehog inhibitor JK184 and the β-catenin inhibitor Prodigiosin. Results CD56 was significantly overexpressed in both human ccRCC tissues and renal cancer cell lines compared to adjacent normal tissues and normal renal epithelial cells. In vitro and in vivo experiments revealed that the knockout of CD56 inhibited the proliferation, migration, and invasion capabilities of ccRCC cells, whereas the overexpression of PSA-CD56 promoted these capacities. Finally, PSA-CD56 overexpression was found to activate both the Hedgehog and Wnt/β-catenin signaling pathways. Conclusion Our findings demonstrate that the oncogenic function of CD56 polysialylation plays a vital role in the tumorigenesis and progression of ccRCC, implying that targeting PSA-CD56 might be a feasible treatment target for ccRCC.

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“…The viability of NPC cells was determined using the cell counting kit‐8 (CCK‐8; EnoGene; Nanjing, China). NPC cells were seeded in a 96‐well plate at a density of 3 × 10 3 cells per well (Li et al, 2022). A stock solution was prepared by dissolving 5 mg of AE in 1.8 ml of dimethyl sulfoxide and diluting it with the complete medium to obtain working solutions of different concentrations (15, 30, 45, 60, and 75 μM).…”

Section: Methodsmentioning

confidence: 99%

Aloe‐emodin targets multiple signaling pathways by blocking ubiquitin‐mediated degradation of DUSP1 in nasopharyngeal carcinoma cells

Chen

Guan

Xie

et al. 2023

Phytotherapy Research

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Aloe‐emodin (AE) has been shown to inhibit the proliferation of several cancer cell lines, including human nasopharyngeal carcinoma (NPC) cell lines. In this study, we confirmed that AE inhibited malignant biological behaviors, including cell viability, abnormal proliferation, apoptosis, and migration of NPC cells. Western blotting analysis revealed that AE upregulated the expression of DUSP1, an endogenous inhibitor of multiple cancer‐associated signaling pathways, resulting in blockage of the extracellular signal‐regulated kinase (ERK)‐1/2, protein kinase B (AKT), and p38‐mitogen activated protein kinase（p38‐MAPK） signaling pathways in NPC cell lines. Moreover, the selective inhibitor of DUSP1, BCI‐hydrochloride, partially reversed the AE‐induced cytotoxicity and blocked the aforementioned signaling pathways in NPC cells. In addition, the binding between AE and DUSP1 was predicted via molecular docking analysis using AutoDock‐Vina software and further verified via a microscale thermophoresis assay. The binding amino acid residues were adjacent to the predicted ubiquitination site (Lys192) of DUSP1. Immunoprecipitation with the ubiquitin antibody, ubiquitinated DUSP1 was shown to be upregulated by AE. Our findings revealed that AE can stabilize DUSP1 by blocking its ubiquitin–proteasome‐mediated degradation and proposed an underlying mechanism by which AE‐upregulated DUSP1 may potentially target multiple pathways in NPC cells.

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Andrographolide suppresses breast cancer progression by modulating tumor‐associated macrophage polarization through the Wnt/β‐catenin pathway

Cited by 14 publications

References 47 publications

The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer

The Effect of Salvianolic Acid A on Tumor-Associated Macrophage Polarization and Its Mechanisms in the Tumor Microenvironment of Triple-Negative Breast Cancer

CD56 polysialylation promotes the tumorigenesis and progression via the Hedgehog and Wnt/β-catenin signaling pathways in clear cell renal cell carcinoma

Aloe‐emodin targets multiple signaling pathways by blocking ubiquitin‐mediated degradation of DUSP1 in nasopharyngeal carcinoma cells

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