Sertraline repositioning: an overview of its potential use as a chemotherapeutic agent after four decades of tumor reversal studies

Baú-Carneiro, João Luiz; Sumida, I; Gallon, Malu; Zaleski, Tânia; Bóia-Ferreira, Marianna; Cavassin, Francelise Bridi

doi:10.1016/j.tranon.2021.101303

Cited by 12 publications

(12 citation statements)

References 64 publications

(201 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition to its use as an antidepressant, SRT has also been explored for other therapeutic applications. In vitro and in vivo studies have demonstrated its potential application in treating osteomyelitis infection [ 38 ] and cancer [ 39 ]. Furthermore, SRT presents antiparasitic [ 40 ], antibacterial [ 41 ], and antifungal activities against various pathogenic fungi, including C. neoformans [ 10 , 11 ], Aspergillus fumigatus [ 7 ], Trichosporon asahii [ 12 ], Sporothrix schenckii [ 9 ], and T. rubrum [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum

Galvão-Rocha

Rocha

Martins

et al. 2023

JoF

View full text Add to dashboard Cite

The dermatophyte Trichophyton rubrum is responsible for most human cutaneous infections. Its treatment is complex, mainly because there are only a few structural classes of fungal inhibitors. Therefore, new strategies addressing these problems are essential. The development of new drugs is time-consuming and expensive. The repositioning of drugs already used in medical practice has emerged as an alternative to discovering new drugs. The antidepressant sertraline (SRT) kills several important fungal pathogens. Accordingly, we investigated the inhibitory mechanism of SRT in T. rubrum to broaden the knowledge of its impact on eukaryotic microorganisms and to assess its potential for future use in dermatophytosis treatments. We performed next-generation sequencing (RNA-seq) to identify the genes responding to SRT at the transcript level. We identified that a major effect of SRT was to alter expression for genes involved in maintaining fungal cell wall and plasma membrane stability, including ergosterol biosynthetic genes. SRT also altered the expression of genes encoding enzymes related to fungal energy metabolism, cellular detoxification, and defense against oxidative stress. Our findings provide insights into a specific molecular network interaction that maintains metabolic stability and is perturbed by SRT, showing potential targets for its strategic use in dermatophytosis.

show abstract

Section: Discussionmentioning

confidence: 99%

The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum

Galvão-Rocha

Rocha

Martins

et al. 2023

JoF

View full text Add to dashboard Cite

show abstract

“…Studies have shown that TCTP was more expressed in high-grade gliomas and indicated worse prognosis, in the adulthood, whereas its expression decreased in tumor reversion phenomena, a biological process in which neoplastic cells lose its malignant phenotype ( Amson et al, 2013 ; Tuynder et al, 2004 ). Moreover, TCTP has been studied as a therapeutic target, and sertraline, an antidepressant, has been shown to inhibit TCTP levels, thus increasing p53 expression, and inducing tumor reversion ( Amson et al, 2013 ; Baú-Carneiro et al, 2022 ; Boia-Ferreira et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas

et al. 2023

View full text Add to dashboard Cite

Central nervous system tumors, especially astrocytomas, are the solid neoplasms with the highest incidence and mortality rates in childhood. The diagnosis is based on histopathological characteristics, but molecular methods have been increasingly used. Translationally controlled tumor protein (TCTP) protein, encoded by the tumor protein, translationally controlled 1 ( TPT1) gene, is a multifunctional protein with an important physiological role in the cell cycle. Expression of this protein has been associated with several neoplasms, including astrocytomas in adults. However, the role of this protein in pediatric astrocytomas is largely unknown. We aim to evaluate in cases of pediatric astrocytomas, the frequency of polymorphisms in the TPT1 gene and other genes associated with its molecular pathways, such as MTOR, MDM2, TP53, and CDKN1A, correlating it with protein expression and clinical variables, in formalin-fixed, paraffin-embedded (FFPE) samples. These samples were submitted to genotyping and immunohistochemistry analyses. The most revealing results refer to the MDM2 gene, rs117039649 [G/C], in which C polymorphic allele was observed only in the glioblastomas ( p = .028). The CDKN1A gene, rs3176334 [T/C] presented a homozygous polymorphic genotype only in high-grade astrocytomas, when infiltrating tumors were compared ( p = .039). The immunohistochemical expression of cytoplasmic MDM2 correlated with better survival rates in patients with glioblastoma ( p = .018). The presence of polymorphisms in the MDM2 and CDKN1A genes, as well as a specific correlation between MDM2 expression, suggests a likely association with risk in pediatric astrocytomas. This study sought the probable role involved in the TCTP pathway, and associated proteins, in the tumorigenesis of pediatric astrocytomas, and some could have potential impact as prognostic markers in these patients.

show abstract

“…Interestingly, downregulation of TCTP has been associated with increased tumour reversion phenotype 8 . TCTP has been reported to be a pharmacological target of clinical drugs Sertraline, Thioridazine and Dihydroartemisinin (DHA) 9,10 . Over the past two decades, TCTP has emerged as an important factor in cancer development, although its role in oral cancer progression has rarely been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…8 TCTP has been reported to be a pharmacological target of clinical drugs Sertraline, Thioridazine and Dihydroartemisinin (DHA). 9,10 Over the past two decades, TCTP has emerged as an important factor in cancer development, although its role in oral cancer progression has rarely been investigated. Thus, the present study attempts to investigate the clinical and functional significance of TCTP expression in oral cancers.…”

Section: Introductionmentioning

confidence: 99%

Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome

Sharma,

Pawar,

Sulkshane

et al. 2023

J Oral Pathology Medicine

View full text Add to dashboard Cite

BackgroundTranslationally controlled tumour protein (TCTP) is a multifunctional protein elevated in multiple cancers. However, studies on its role in oral carcinogenesis and prognosis are rare. We recently reported the role of its interacting partner, MCL1, in oral cancer progression and outcome. Hence, the present study aimed to assess TCTP expression in oral tumorigenesis and its association with patient outcomes alone and in combination with MCL1.MethodsTCTP expression was assessed by immunohistochemistry and immunoblotting in oral tissues and cells, respectively. Cell viability post siRNA/dihydroartemisinin treatment was analysed by tetrazolium salt assay. Cell survival, invasion and tumorigenic potential post TCTP knockdown were assessed by clonogenic, Matrigel and soft‐agar assays, respectively. The association of TCTP with patient outcome was analysed by Kaplan–Meier and Cox regression.ResultsTCTP was significantly overexpressed in oral premalignant lesions (p < 0.0001), oral tumours (p < 0.0001) and oral dysplastic and cancer cells versus normal oral mucosa and also in recurrent (p < 0.05) versus non‐recurrent oral tumours. Further, elevated TCTP was significantly (p < 0.05) associated with poor recurrence free survival (RFS) and poor overall survival (OS; hazard ratio = 2.29; p < 0.05). Intriguingly, the high co‐expression of TCTP and MCL1 further reduced the RFS (p < 0.05) and OS (p < 0.05; hazard‐ratio = 3.49; p < 0.05). Additionally, TCTP knockdown decreased survival (p < 0.05), invasion (p < 0.01) and in vitro tumorigenic potential (p < 0.0001). Dihydroartemisinin treatment reduced TCTP levels and viability of oral cancer cells.ConclusionOur studies demonstrate an oncogenic role of TCTP in oral cancer progression and poor outcome. Thus, TCTP may be a potential prognostic marker and therapeutic target in oral cancers.

show abstract

Sertraline repositioning: an overview of its potential use as a chemotherapeutic agent after four decades of tumor reversal studies

Cited by 12 publications

References 64 publications

The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum

The Antidepressant Sertraline Affects Cell Signaling and Metabolism in Trichophyton rubrum

Polymorphisms in TPT1 Pathways in Pediatric Astrocytomas

Elevated translationally controlled tumour protein promotes oral cancer progression and poor outcome

Contact Info

Product

Resources

About