Discovery of CCL18 antagonist blocking breast cancer metastasis

Liu, Yujie; Zheng, Huaqin; Li, Qian; Li, Shunying; Lai, Hongna; Song, Erwei; Ding, Li; Chen, Jingqi

doi:10.1007/s10585-019-09965-2

Cited by 23 publications

(21 citation statements)

References 36 publications

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“…This is the result of genetic instability and selective pressure due to adverse conditions of the tumor microenvironment [81,82]. For this reason, therapy directed against only one chemokine may not give the desired results [267]. Another problem is the involvement of cancer processes in anti-cancer mechanisms.…”

Section: Cancer Therapy Targeting the Entire Hypoxic Microenvironmentmentioning

confidence: 99%

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Korbecki

Kojder

Barczak

et al. 2020

IJMS

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Hypoxia, i.e., oxygen deficiency condition, is one of the most important factors promoting the growth of tumors. Since its effect on the chemokine system is crucial in understanding the changes in the recruitment of cells to a tumor niche, in this review we have gathered all the available data about the impact of hypoxia on β chemokines. In the introduction, we present the chronic (continuous, non-interrupted) and cycling (intermittent, transient) hypoxia together with the mechanisms of activation of hypoxia inducible factors (HIF-1 and HIF-2) and NF-κB. Then we describe the effect of hypoxia on the expression of chemokines with the CC motif: CCL1, CCL2, CCL3, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL24, CCL25, CCL26, CCL27, CCL28 together with CC chemokine receptors: CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10. To better understand the effect of hypoxia on neoplastic processes and changes in the expression of the described proteins, we summarize the available data in a table which shows the effect of individual chemokines on angiogenesis, lymphangiogenesis, and recruitment of eosinophils, myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and tumor-associated macrophages (TAM) to a tumor niche.

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Section: Cancer Therapy Targeting the Entire Hypoxic Microenvironmentmentioning

confidence: 99%

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Korbecki

Kojder

Barczak

et al. 2020

IJMS

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“…In this way, 15 compounds were selected as potential drugs targeting CCL18, and the toxicity of these 15 compounds was evaluated by using cell counting kit-8 (CCK-8) assays, which indicated that most of the compounds did not influence cell viability. A total of 6 of the 15 compounds inhibited CCL18-induced cell migration; this anticancer activity was also confirmed by adherence and invasion assays [19].…”

Section: Systematic Repositioning Of Drugs/moleculesmentioning

confidence: 70%

“…In a recent study, Liu et al screened more than 1000 known small molecular compounds and focused on 15 compounds [19], studying their effect on breast cancer cell viability and migration with in vitro studies on MCF-7, MDA-MB-231, and BT-474 BC cell lines. Molecular docking was performed to demonstrate the ability of the binding of the 15 compounds with chemokine ligand 18 (CCL18), as previous studies suggested that CCL18 is a chemokine derived from tumor-associated macrophages (TAMs) to induce BC metastasis [20].…”

Section: Systematic Repositioning Of Drugs/moleculesmentioning

confidence: 99%

Integration of Molecular Docking and In Vitro Studies: A Powerful Approach for Drug Discovery in Breast Cancer

Cava

Castiglioni

2020

Applied Sciences

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Molecular docking in the pharmaceutical industry is a powerful in silico approach for discovering novel therapies for unmet medical needs predicting drug–target interactions. It not only provides binding affinity between drugs and targets at the atomic level, but also elucidates the fundamental pharmacological properties of specific drugs. The purpose of this review was to illustrate newer and emergent uses of docking when combined with in vitro techniques for drug discovery in metastatic breast cancer. We grouped the selected articles into five main categories; namely, systematic repositioning of drugs, natural drugs, new synthesized molecules, combinations of drugs, and drug latentiation. We focused on new promising drugs that have a good affinity with their targets, thus inducing a favorable biological response. This review suggests that the integration of molecular docking and in vitro studies can accelerate cancer drug discovery showing a good consistency of the results between the two approaches.

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“…It is believed that use of drugs or natural compounds that can suppress oncogenic cytokines (e.g., CXCL1, CCL18, CCL8, CCL2, IL-4, IL-8, IL-6, etc.) (17,(48)(49)(50)(51)(52)(53) such as apigenin, EGCG or butein can curtail these biochemical driven events and provide therapeutic advantages against aggressive inflammatory breast cancers (54,55).…”

Section: Discussionmentioning

confidence: 99%

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

et al. 2020

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The lack of hormone receptors in triple negative breast cancer (TNBC) is associated with the inefficacy of anti-estrogen chemotherapies, leaving fewer options for patient treatment and higher mortality rates. Additionally, as with numerous types of inflammatory breast cancer, infiltration of tumor associated macrophages and other leukocyte sub-populations within the tumor inevitably lead to aggressive, chemo-resistant, metastatic and invasive types of cancer which escape immune surveillance. These processes are orchestrated by the release of potent cytokines, including TNFα, IL-6 and CCL2 from the stroma, tumor and immune cells within the tumor microenvironment. The present study evaluated apigenin modulating effects on the pro-inflammatory activating action of TNFα in TNBC MDA-MB-468 cells, derived from an African American woman. Initially, cell viability was determined to establish an optimal sub-lethal dose of TNFα and apigenin in MDA-MB-468 cells. Subsequently, various treatments effects were evaluated using whole transcriptomic analysis of mRNA and long intergenic non-coding RNA with Affymetrix HuGene-2.1-st human microarrays. Gene level differential expression analysis was conducted on 48,226 genes where TNFα caused significant upregulation of 53 transcripts and downregulation of 11 transcripts. The largest upward differential shift was for CCL2 [+61.86 fold change (FC); false discovery rate (FDR), P<0.0001]; which was down regulated by apigenin (to +10.71 FC vs. Control; FDR P-value <0.001), equivalent to an 83% reduction. Several TNFα deferentially upregulated transcripts were reduced by apigenin, including CXCL10, C3, PGLYRP4, IL22RA2, KMO, IL7R, ROS1, CFB, IKBKe, SLITRK6 (a checkpoint target) and MMP13. Confirmation of CCL2 experimentally induced transcript alterations was corroborated at the protein level by ELISA assays. The high level of CCL2 transcript in the cell line was comparable to that in our previous studies in MDA-MB-231 cells. The differential effects of TNFα were corroborated by ELISA, where the data revealed a >10-fold higher releasing rate of CCL2 in MDA-MB-468 cells compared with in MDA-MB-231 cells, both of which were attenuated by apigenin. The data obtained in the present study demonstrated a high level of CCL2 in MDA-MB-468 cells and a possible therapeutic role for apigenin in downregulating TNFα-mediated processes in these TNBC cells.

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Discovery of CCL18 antagonist blocking breast cancer metastasis

Cited by 23 publications

References 36 publications

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Hypoxia Alters the Expression of CC Chemokines and CC Chemokine Receptors in a Tumor–A Literature Review

Integration of Molecular Docking and In Vitro Studies: A Powerful Approach for Drug Discovery in Breast Cancer

Effect of apigenin on whole transcriptome profile of TNFα‑activated MDA‑MB‑468 triple negative breast cancer cells

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