Effects of Tamoxifen on Periodontal Disease and
            <i>Candida Albicans</i>
            of Patients with Breast Cancer and Other Pathologies

Muthular, Milagros; Bálsamo, Fernanda; Passero, Pablo; Jewtuchowicz, Virginia; Miozza, Valeria; Villalba, M. Blanco; Brusca, María Isabel; Pérez, Cristina

doi:10.2217/fmb-2018-0272

Cited by 12 publications

(11 citation statements)

References 23 publications

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“…Clinical isolates of fluconazole-sensitive and resistance C. albicans from patients with periodontal disease revealed in vitro inhibition by TAM. 23 In comparison with imidazole, TAM showed fungicidal action against C. albicans at low concentration (15-20 µM), especially at stationary phase of yeast growth. 24 Whereas, the MIC range may become higher (8-64 g/mL) for Cryptococcus neoformans and other isolates of Candida spp.…”

Section: Tamoxifen As An Anti-fungal Drugmentioning

confidence: 99%

Tamoxifen: From Anti-cancer to Antifungal Drug

2019

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Tamoxifen (TAM) is an important drug for treatment of breast cancer. It is most effective against estrogen receptor-positive and negative breast cancer. Protective adjuvant is another applied of TAM for women at risk of development of breast cancer. Anti-cancer activity of TAM can take various pathways of action. Antagonistic with estrogen receptor and oxidation reaction are the most proposed mechanism of action of TAM in cancer cells. Recently, many studies focused on the potential antimicrobial action of TAM. Fungi are demonstrated to affect by TAM through various mechanism of action. Yeasts, especially Candida albicans, are the most common type of fungi used to test the antifungal action of TAM. Inhibitory action on some components of the calcium-calcineurin pathway in fungal cells is most acceptable mechanism of TAM action. TAM can also play a synergistic role to increase the antifungal activity of other standard agents. This review will discuss the most recent information about antifungal action of TAM.

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Section: Tamoxifen As An Anti-fungal Drugmentioning

confidence: 99%

Tamoxifen: From Anti-cancer to Antifungal Drug

2019

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“…17,18 Moreover, evidence of improved disease outcomes following antifungal measures has been observed and suggests a role for C. albicans in contributing to disease pathology. Examples include tamoxifen-induced C. albicans inhibition to reduce severity of periodontitis in women, 46 as well as fluconazole treatment 47 or faecal microbiota transplantation (inhibiting C. albicans burdens) 48 to rescue ulcerative colitis symptoms in mice. There are also limited reports of improved C. albicans-related respiratory diseases following fluconazole administration 15,49 (though Aspergillus species have been better studied in airways disease 50,51 ).…”

Section: Il-17-mediated Disordersmentioning

confidence: 99%

Candida albicans and candidalysin in inflammatory disorders and cancer

Camilli

Griffiths

et al. 2020

Immunology

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Summary As our understanding of mycology progresses, the impact of fungal microbes on human health has become increasingly evident. Candida albicans is a common commensal fungus that gives rise to local and systemic infections, particularly in immunocompromised patients where it can result in mortality. However, C. albicans has also been quietly linked with a variety of inflammatory disorders, to which it has traditionally been considered incidental; recent studies may now provide new aspects of these relationships for further consideration. This review provides a novel perspective on the impact of C. albicans and its peptide toxin, candidalysin, on human health, exploring their contributions to pathology within a variety of diseases.

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“…We and other researchers found that TAM potentiates the activity of existing antifungal drugs, such as azoles, terbinafine, polyenes, and echinocandins, in diverse fungal species (7,10). More recently, it has been reported that TAM inhibits the growth of clinical C. albicans strains of the oral cavity as well as well-characterized azole-resistant C. albicans strains isolated from an immunocompromised patient (11). Furthermore, a randomized clinical trial showed initial efficacy and safety data for TAM combined with antifungals, including amphotericin B and fluconazole, in HIV-infected or uninfected adults with cryptococcal meningitis (12).…”

mentioning

confidence: 91%

NADPH-Cytochrome P450 Reductase Ccr1 Is a Target of Tamoxifen and Participates in Its Antifungal Activity via Regulating Cell Wall Integrity in Fission Yeast

Liu

Guo

Jiang

et al. 2020

Antimicrob Agents Chemother

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Invasive fungal diseases are a leading cause of mortality among immune-compromised populations. Treatment is notoriously difficult due to the limited number of antifungal drugs as well as the emergence of drug resistance. Tamoxifen (TAM), a selective estrogen receptor modulator frequently used for treatment of breast cancer, has been found to have antifungal activities, and may be a useful addition to treat fungal infectious diseases. However, its molecular mechanisms underlying the antifungal actions remain obscure. Here, we screened for mutations that conferred sensitivity to antifungal drug azoles by using fission yeast as a model, and isolated the cls1 (ccr1) mutant, an allele of the gene encoding NADPH-cytochrome P450 reductase Ccr1. We found that deletion of ccr1+ gene exhibited hypersensitivities to various drugs, including antifungal drugs azoles, terbinafine, micafungin, immunosuppressor FK506, anticancer drugs TAM and 5-fluorouracil (5-FU). Unexpectedly, overexpression of Ccr1 caused yeast cells resistance to TAM, but not the other drugs tested here. Additionally, deletion of Ccr1 displayed pleiotropic phenotypes, including defects in cell wall integrity and vacuole fusion, enhanced calcineurin activity as well as increased intracellular Ca2+ levels. Overexpression of the constitutively active calcineurin suppressed the drug sensitive phenotypes of the Δccr1 cells. Notably, TAM treatment on wild-type cells resulted in pleiotropic phenotypes, similar to that of Ccr1 lacking. Furthermore, TAM inhibited NADPH-cytochrome P450 reductase activities Ccr1 activity in a dose-dependent manner. Moreover, TAM treatment also inhibited NADPH-cytochrome P450 reductase activities of Candida albicans and resulted in defective cell wall integrity. Collectively, our findings suggest that Ccr1 is a novel target of TAM and is involved in the antifungal activity of TAM through regulating cell wall integrity in fission yeast.

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Effects of Tamoxifen on Periodontal Disease and Candida Albicans of Patients with Breast Cancer and Other Pathologies

Cited by 12 publications

References 23 publications

Tamoxifen: From Anti-cancer to Antifungal Drug

Tamoxifen: From Anti-cancer to Antifungal Drug

Candida albicans and candidalysin in inflammatory disorders and cancer

NADPH-Cytochrome P450 Reductase Ccr1 Is a Target of Tamoxifen and Participates in Its Antifungal Activity via Regulating Cell Wall Integrity in Fission Yeast

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