Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers

Avendaño-Félix, Mariana; Aguilar‐Medina, Maribel; Bermúdez, Mercedes; Lizárraga-Verdugo, Erik; López-Camarillo, César; Ramos‐Payán, Rosalío

doi:10.3389/fonc.2020.01452

Cited by 5 publications

(5 citation statements)

References 65 publications

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“…The anticancer properties of antidepressant drugs in adjuvant cancer therapy have been previously reported [19,20]. Although, previous data support the beneficial role of antidepressant drugs in glioma, the molecular mechanisms involved in these drugs have not been established.…”

Section: Discussionmentioning

confidence: 98%

Glucuronidase beta is an early predictive marker for the use of antidepressant in the treatment of glioma patients

Xu¹,

Chen²

2022

Trop. J. Pharm Res

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Purpose: To screen early targets and investigate the potential molecular mechanisms involved in the use of antidepressant in the treatment of glioma. Methods: The GSE89873 dataset, including expression levels of C6 cells under antidepressant treatment, non-antidepressant drug treatment, and untreated cells (control), was downloaded from database. Differentially expressed genes (DEGs) between antidepressant treatment and untreated cells, and between non-antidepressant drug treatment and untreated cells were identified and annotated. Genes that were significantly related to different drug treatment conditions were screened. Results: In all, 416 differentially expressed genes (DEGs) were selected between cells of the antidepressant treatment and control groups, while 650 DEGs were selected between cells of the non-antidepressant treatment and control groups. The 402 overlapping DEGs were significantly associated with the apoptotic process, transforming growth factor beta receptor signaling pathway, and cell cycle arrest (p < 0.05). The DEGs ACOX1, ACSL1, GSTM3, and GSTP1 were significantly related to hormonal therapy (p < 0.05). Glucuronidase beta (GUSB) was significantly associated with age and targeted molecular therapy (p < 0.05). The GUSB was also significantly associated with overall survival time (p < 0.05). It is one of the unique DEGs in the antidepressant treatment group that participates in the drug metabolism-cytochrome P450 metabolic pathway. Conclusion: Glucuronidase beta may be a specific biomarker for the early response of antidepressants to glioma treatment. This should, however, be further investigated to validate this finding.

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Section: Discussionmentioning

confidence: 98%

Glucuronidase beta is an early predictive marker for the use of antidepressant in the treatment of glioma patients

Xu¹,

Chen²

2022

Trop. J. Pharm Res

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“…These results are particularly interesting as it has recently been shown that psychiatric drugs offer potential as anti-cancer therapeutics ( Loehr et al, 2021 ). Moreover, a recent review has specifically addressed the need to investigate psychiatric drugs for treatment of gastrointestinal cancers ( Avendaño-Félix et al, 2020 ). We hypothesise that Crizotinib, Lapatinib, and Dasatinib are amongst the drugs with the most potential.…”

Section: Discussionmentioning

confidence: 99%

Drug repositioning for esophageal squamous cell carcinoma

Bennett

Huang

et al. 2022

Front. Genet.

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Esophageal cancer (EC) remains a significant challenge globally, having the 8th highest incidence and 6th highest mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common form of EC in Asia. Crucially, more than 90% of EC cases in China are ESCC. The high mortality rate of EC is likely due to the limited number of effective therapeutic options. To increase patient survival, novel therapeutic strategies for EC patients must be devised. Unfortunately, the development of novel drugs also presents its own significant challenges as most novel drugs do not make it to market due to lack of efficacy or safety concerns. A more time and cost-effective strategy is to identify existing drugs, that have already been approved for treatment of other diseases, which can be repurposed to treat EC patients, with drug repositioning. This can be achieved by comparing the gene expression profiles of disease-states with the effect on gene-expression by a given drug. In our analysis, we used previously published microarray data and identified 167 differentially expressed genes (DEGs). Using weighted key driver analysis, 39 key driver genes were then identified. These driver genes were then used in Overlap Analysis and Network Analysis in Pharmomics. By extracting drugs common to both analyses, 24 drugs are predicted to demonstrate therapeutic effect in EC patients. Several of which have already been shown to demonstrate a therapeutic effect in EC, most notably Doxorubicin, which is commonly used to treat EC patients, and Ixazomib, which was recently shown to induce apoptosis and supress growth of EC cell lines. Additionally, our analysis predicts multiple psychiatric drugs, including Venlafaxine, as repositioned drugs. This is in line with recent research which suggests that psychiatric drugs should be investigated for use in gastrointestinal cancers such as EC. Our study shows that a drug repositioning approach is a feasible strategy for identifying novel ESCC therapies and can also improve the understanding of the mechanisms underlying the drug targets.

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“…In colorectal cancer (CRC), PMTZ not only suppresses the proliferation of cancer cells but also initiates mitochondrial apoptosis through the PI3K/AKT pathway (61). Additionally, research has illuminated PMTZ's capacity to induce autophagy in pancreatic ductal adenocarcinoma (PDAC), where it functions as an antagonist of proliferation (62). Furthermore, PMTZ has demonstrated a potent inhibitory impact on the proliferation of both human and murine…”

Section: Promethazine (Pmtz)mentioning

confidence: 99%

“…Initiating of autophagy-associated apoptosis through AMPK activation and PI3K/AKT/mTOR inhibition (60), promotes apoptosis by suppressing the PI3K/AKT signaling pathway (61), hinders proliferation and induces autophagy by increasing LC3II and p62 levels in cancer cell lines (62).…”

Section: Promethazinementioning

confidence: 99%

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Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells

Mehrabi,

Elmi,

Nylandsted

2023

Front. Oncol.

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The limitations of current cancer therapies, including the increasing prevalence of multidrug resistance, underscore the urgency for more effective treatments. One promising avenue lies in the repurposing of existing drugs. This review explores the impact of phenothiazines, primarily used as antipsychotic agents, on key mechanisms driving tumor growth and metastasis. The cationic and amphiphilic nature of phenothiazines allows interaction with the lipid bilayer of cellular membranes, resulting in alterations in lipid composition, modulation of calcium channels, fluidity, thinning, and integrity of the plasma membrane. This is especially significant in the setting of increased metabolic activity, a higher proliferative rate, and the invasiveness of cancer cells, which often rely on plasma membrane repair. Therefore, properties of phenothiazines such as compromising plasma membrane integrity and repair, disturbing calcium regulation, inducing cytosolic K-RAS accumulation, and sphingomyelin accumulation in the plasma membrane might counteract multidrug resistance by sensitizing cancer cells to membrane damage and chemotherapy. This review outlines a comprehensive overview of the mechanisms driving the anticancer activities of phenothiazines derivates such as trifluoperazine, prochlorperazine, chlorpromazine, promethazine, thioridazine, and fluphenazine. The repurposing potential of phenothiazines paves the way for novel approaches to improve future cancer treatment.

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Refocusing the Use of Psychiatric Drugs for Treatment of Gastrointestinal Cancers

Cited by 5 publications

References 65 publications

Glucuronidase beta is an early predictive marker for the use of antidepressant in the treatment of glioma patients

Glucuronidase beta is an early predictive marker for the use of antidepressant in the treatment of glioma patients

Drug repositioning for esophageal squamous cell carcinoma

Repurposing phenothiazines for cancer therapy: compromising membrane integrity in cancer cells

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