Improved survival in several cancers with use of H1-antihistamines desloratadine and loratadine

Fritz, Ildikó; Wagner, Philippe; Olsson, Håkan

doi:10.1016/j.tranon.2021.101029

Cited by 43 publications

(24 citation statements)

References 52 publications

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“…Interestingly, intestinal bacteria‐derived local histamine suppressed colorectal cancer progression, 24 whereas prostate histamine, increased due to HFD intake, promoting cancer growth in this study. In the epidemiological research, administration of desloratadine, an H1 receptor antagonist, reduces the hazard ratio for prostate cancer to 0.75, whereas the H2 receptor antagonists cimetidine and Rani do not have the same preventive effects 25,26 . The findings of this animal study may be beneficial in developing a new prostate cancer treatment strategy that is safe and inexpensive, with drug repositioning.…”

Section: Discussionmentioning

confidence: 82%

“…In the epidemiological research, administration of desloratadine, an H1 receptor antagonist, reduces the hazard ratio for prostate cancer to 0.75, whereas the H2 receptor antagonists cimetidine and do not have the same preventive effects. 25,26 The findings of this animal study may be beneficial in developing a new prostate cancer treatment strategy that is safe and inexpensive, with drug repositioning.…”

Section: Discussionmentioning

confidence: 98%

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High‐fat diet promotes prostate cancer growth through histamine signaling

Matsushita

Fujita

Hatano

et al. 2022

Intl Journal of Cancer

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Western high‐fat diets (HFD) are regarded as a major risk factor for prostate cancer (PCa). Using prostate‐specific Pten‐knockout mice as a PCa model, we previously reported that HFD promoted inflammatory PCa growth. The composition of the gut microbiota changes under the influence of diet exert various effects on the host through immunological mechanisms. Herein, we investigated the etiology of HFD‐induced inflammatory cancer growth and the involvement of the gut microbiome. The expression of Hdc, the gene responsible for histamine biosynthesis, and histamine levels were upregulated in large prostate tumors of HFD‐fed mice, and the number of mast cells increased around the tumor foci. Administration of fexofenadine, a histamine H1 receptor antagonist, suppressed tumor growth in HFD‐fed mice by reducing the number of myeloid‐derived suppressor cells and suppressing IL6/STAT3 signaling. HFD intake induced gut dysbiosis, resulting in the elevation of serum lipopolysaccharide (LPS) levels. Intraperitoneal injection of LPS increased Hdc expression in PCa. Inhibition of LPS/Toll‐like receptor 4 signaling suppressed HFD‐induced tumor growth. The number of mast cells increased around the cancer foci in total prostatectomy specimens of severely obese patients. In conclusion, HFD promotes PCa growth through histamine signaling via mast cells. Dietary high‐fat induced gut dysbiosis might be involved in the inflammatory cancer growth.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 98%

High‐fat diet promotes prostate cancer growth through histamine signaling

Matsushita

Fujita

Hatano

et al. 2022

Intl Journal of Cancer

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“…The usefulness of determining the level of biogenic amines has been described in the case of the diagnosis of Parkinson’s disease [ 23 ] and central nervous system infections such as bacterial and viral meningitis [ 24 ], the pathophysiology of schizophrenia spectrum disorders and the impact of antipsychotic treatment [ 25 ], the importance of vaginal bacteria in bacterial vaginosis [ 26 ], a better understanding of inflammatory bowel diseases [ 27 ], and the diagnosis of early ischemic stroke [ 25 ]. It is also helpful in the early diagnosis of neuroendocrine tumors [ 28 ], in the development of new methods of examining neoplastic cells [ 29 ], or in new therapies targeting biogenic amines, including those based on the use of antihistamines [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer

Czerwiński

Bednarska-Czerwińska

Zmarzły³

et al. 2021

JCM

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Biogenic amines, such as adrenaline, noradrenaline, histamine, dopamine, and serotonin are important neurotransmitters that also regulate cell viability. Their detection and analysis are helpful in the diagnosis of many diseases, including cancer. The aim of this study was to determine the expression profile of the biogenic amine-related genes and proteins in endometrioid endometrial cancer compared to the control group. The material consisted of endometrial tissue samples and whole blood collected from 30 endometrioid endometrial cancer patients and 30 cancer-free patients. The gene expression was determined by the mRNA microarrays and validated by qRT-PCR. Protein levels were determined in the serum by the enzyme-linked immunosorbent assay (ELISA). Overexpression of histamine H1–H3 receptors and early growth response 1 and silencing of calmodulin, the histamine H4 receptor, and the dopamine D5 receptor have been reported in endometrioid endometrial cancer. The obtained results indicate disturbances in the signaling activated by histamine and dopamine receptors, which could potentially contribute to the progression of endometrioid endometrial cancer.

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“…Desloratadine is an antihistaminic drug that suppresses allergic reactions, e.g., urticaria, rhinitis, and allergic inflammatory diseases [ 37 , 38 ]. Remarkably, desloratadine has been also reported to improve the survival time of patients suffering from melanoma or breast cancer [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Anthracycline Resistance Genes and Their Inhibitors

et al. 2021

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Differentially expressed genes have been previously identified by us in multidrug-resistant tumor cells mainly resistant to doxorubicin. In the present study, we exemplarily focused on some of these genes to investigate their causative relationship with drug resistance. HMOX1, NEIL2, and PRKCA were overexpressed by lentiviral-plasmid-based transfection of HEK293 cells. An in silico drug repurposing approach was applied using virtual screening and molecular docking of FDA-approved drugs to identify inhibitors of these new drug-resistant genes. Overexpression of the selected genes conferred resistance to doxorubicin and daunorubicin but not to vincristine, docetaxel, and cisplatin, indicating the involvement of these genes in resistance to anthracyclines but not to a broader MDR phenotype. Using virtual drug screening and molecular docking analyses, we identified FDA-approved compounds (conivaptan, bexarotene, and desloratadine) that were interacting with HMOX1 and PRKCA at even stronger binding affinities than 1-(adamantan-1-yl)-2-(1H-imidazol-1-yl)ethenone and ellagic acid as known inhibitors of HMOX1 and PRKCA, respectively. Conivaptan treatment increased doxorubicin sensitivity of both HMOX1- and PRKCA-transfected cell lines. Bexarotene treatment had a comparable doxorubicin-sensitizing effect in HMOX1-transfected cells and desloratadine in PRKCA-transfected cells. Novel drug resistance mechanisms independent of ABC transporters have been identified that contribute to anthracycline resistance in MDR cells.

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Improved survival in several cancers with use of H1-antihistamines desloratadine and loratadine

Cited by 43 publications

References 52 publications

High‐fat diet promotes prostate cancer growth through histamine signaling

High‐fat diet promotes prostate cancer growth through histamine signaling

Evaluation of the Differences in the Expression of Biogenic Amine-Related mRNAs and Proteins in Endometrioid Endometrial Cancer

Identification of Novel Anthracycline Resistance Genes and Their Inhibitors

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