Clotrimazole presents anticancer properties against a mouse melanoma model acting as a PI3K inhibitor and inducing repolarization of tumor-associated macrophages

Ochioni, Alan Clavelland; Filho, Ricardo Imbroisi; Esteves, Amanda M.; Leandro, João G. B.; Demaria, Thainá M.; Júnior, José Xavier do Nascimento; Pereira-Dutra, Filipe; Bozza, Patrı́cia T.; Sola‐Penna, Mauro; Zancan, Patrícia

doi:10.1016/j.bbadis.2021.166263

Cited by 12 publications

(4 citation statements)

References 46 publications

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“…have reported similar antitumor effects, in studies performed in vitro on tumor cell lines type A549 (human lung adenocarcinoma), HT-29 (human colon adenocarcinoma), MM-RU (human melanoma), and B16-F1-36 (mice melanoma) [ 28 ]. Proapoptotic effects on melanoma tumor cell lines were and continue to be also reported by other researchers [ 29 , 30 , 31 ].…”

Section: Introductionsupporting

confidence: 82%

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene

et al. 2022

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The paper presents the results of the studies performed to establish the effect of the mixtures between limonene and clotrimazole against microbial pathogens involved in dermatological diseases, such as Candida albicans, Staphyloccocus aureus, and Escherichia coli. Preliminary data obtained from the studies performed in microplates revealed a possible synergism between the mixture of clotrimazole and limonene for Staphylococcus aureus. Studies performed “in silico” with programs such as CLC Drug Discovery Workbench and MOLEGRO Virtual Docker, gave favorable scores for docking each compound on a specific binding site for each microorganism. The tests performed for validation, with the clotrimazole (0.1%) and different sources of limonene (1.9% citrus essential oils), showed a synergistic effect on Staphylococcus aureus in the case of the mixtures between clotrimazole and the essential oils of Citrus reticulata or Citrus paradisi. The studies performed on Staphylococcus aureus MRSA showed a synergistic effect between clotrimazole and the essential oils obtained from Citrus bergamia, Citrus aurantium, or Citrus paradisi. In the case of Pseudomonas aeruginosa, essential oils and clotrimazole used alone did not exhibit antimicrobial activities, but the mixtures between clotrimazole and the essential oils of Citrus bergamia or Citrus sinensis exhibited a synergistic antimicrobial effect.

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Section: Introductionsupporting

confidence: 82%

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene

et al. 2022

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“…1 ). Among these, metabolites are classical non-protein ligands that play significant roles in cell-to-cell interactions [ 45 – 48 ]. For instance, the interaction between tumor-derived histamine and macrophage histamine receptor H1 (HRH1) can lead to T cell dysfunction [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

Predicting intercellular communication based on metabolite-related ligand-receptor interactions with MRCLinkdb

Zhang,

Yang,

Ren

et al. 2024

BMC Biol

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Background Metabolite-associated cell communications play critical roles in maintaining human biological function. However, most existing tools and resources focus only on ligand-receptor interaction pairs where both partners are proteinaceous, neglecting other non-protein molecules. To address this gap, we introduce the MRCLinkdb database and algorithm, which aggregates and organizes data related to non-protein L-R interactions in cell-cell communication, providing a valuable resource for predicting intercellular communication based on metabolite-related ligand-receptor interactions. Results Here, we manually curated the metabolite-ligand-receptor (ML-R) interactions from the literature and known databases, ultimately collecting over 790 human and 670 mouse ML-R interactions. Additionally, we compiled information on over 1900 enzymes and 260 transporter entries associated with these metabolites. We developed Metabolite-Receptor based Cell Link Database (MRCLinkdb) to store these ML-R interactions data. Meanwhile, the platform also offers extensive information for presenting ML-R interactions, including fundamental metabolite information and the overall expression landscape of metabolite-associated gene sets (such as receptor, enzymes, and transporter proteins) based on single-cell transcriptomics sequencing (covering 35 human and 26 mouse tissues, 52 human and 44 mouse cell types) and bulk RNA-seq/microarray data (encompassing 62 human and 39 mouse tissues). Furthermore, MRCLinkdb introduces a web server dedicated to the analysis of intercellular communication based on ML-R interactions. MRCLinkdb is freely available at https://www.cellknowledge.com.cn/mrclinkdb/. Conclusions In addition to supplementing ligand-receptor databases, MRCLinkdb may provide new perspectives for decoding the intercellular communication and advancing related prediction tools based on ML-R interactions.

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“…T lymphocytes play crucial roles in identifying and eradicating tumor cells [22]. Macrophages fulfill vital functions in tumor formation, development, and cell apoptosis and can be categorized into these two main types: M1 macrophages (classically activated) and M2 macrophages (alternatively activated) [23]. Natural killer (NK) cells belong to the innate immune system and possess both anticancer and proinflammatory responses to tumor cells with rare off-target toxicities [24].…”

Section: Introductionmentioning

confidence: 99%

Systemic Immunomodulatory Effects of Codonopsis pilosula Glucofructan on S180 Solid-Tumor-Bearing Mice

Fan,

Long,

Gong

et al. 2023

IJMS

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The immune functions of the body are intricately intertwined with the onset and advancement of tumors, and immunotherapy mediated by bioactive compounds has exhibited initial effectiveness in overcoming chemotherapy resistance and inhibiting tumor growth. However, the comprehensive interpretation of the roles played by immunologic components in the process of combating tumors remains to be elucidated. In this study, the Codonopsis pilosula glucofructan (CPG) prepared in our previous research was employed as an immunopotentiator, and the impacts of CPG on both the humoral and cellular immunity of S180 tumor-bearing mice were investigated. Results showed that CPG administration of 100 mg/kg could effectively inhibit tumor growth in mice with an inhibitory ratio of 45.37% and significantly improve the expression of Interleukin-2 (IL-2), Interferon-γ (IFN-γ), and Tumor Necrosis Factor-α (TNF-α). Additionally, CPG clearly enhanced B-cell-mediated humoral immunity and immune-cell-mediated cellular immunity, and, finally, induced S180 cell apoptosis by arresting cells in the G0/G1 phase, which might result from the IL-17 signaling pathway. These data may help to improve comprehension surrounding the roles of humoral and cellular immunity in anti-tumor immune responses.

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Clotrimazole presents anticancer properties against a mouse melanoma model acting as a PI3K inhibitor and inducing repolarization of tumor-associated macrophages

Cited by 12 publications

References 46 publications

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene

Studies Regarding the Antimicrobial Behavior of Clotrimazole and Limonene

Predicting intercellular communication based on metabolite-related ligand-receptor interactions with MRCLinkdb

Systemic Immunomodulatory Effects of Codonopsis pilosula Glucofructan on S180 Solid-Tumor-Bearing Mice

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