Effects of FOXM1 inhibition and ionizing radiation on melanoma cells

Lee, Vivienne S.; McRobb, Lucinda S.; Moutrie, Vaughan; Santos, Estavam D.; Siu, Timothy L.

doi:10.3892/ol.2018.9482

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…After comprehensively considering the AUC values of the models constructed by diverse algorithms, in this study, the LASSO regression analysis and stepwise multivariate Cox regression analysis were applied to establish the CIAI signature. The study by SIU et al found that radiation combined with FOXM1 inhibition was a potent inducer of cell death and suppressor of migration in metastatic melanoma cells ( Lee et al, 2018 ). A previous study by Bergamasch et al has shown that TP63 inhibits p53-induced apoptosis in melanoma cells following the application of genotoxic drugs, which may serve as a strategy to overcome resistance ( Patel et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma

Zhan

Tan

et al. 2022

Front. Pharmacol.

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Background: Melanoma is the most lethal, and one of the most aggressive forms of cutaneous malignancies, which poor response to treatment has always puzzled clinicians. As is known to all, aging and immune microenvironment are two crucial factors impacting melanoma biological progress through the tumor microenvironment (TME). However, reliable biomarkers for predicting melanoma prognosis based on aging and immune microenvironment and therapeutic efficacy of immune checkpoints remain to be determined.Methods: The aging-related genes (ARGs) were obtained from the Human Ageing Genomic Resources and immune-related genes (IRGs) were downloaded from the Immunology database as well as Analysis Portal (ImmPort) database. Next, we initially performed LASSO regression and multivariate Cox regression to identify prognostic ARGs and IRGs in the TCGA and GSE65904 datasets, and firstly constructed a novel comprehensive index of aging and immune (CIAI) signature. Finally, in vitro molecular biology experiments were performed to assess the regulatory role of CNTFR in melanoma cell lines proliferation and migration, macrophage recruitment, and M2 polarization.Results: This novel CIAI signature consisted of 7 genes, including FOXM1, TP63, ARNTL, KIR2DL4, CCL8, SEMA6A, and CNTFR, in which melanoma patients in the high-CIAI group had shorter OS, DSS, and PFI, indicating CIAI model served as an independent prognostic index. Moreover, we found the CIAI score was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Finally, CNTFR might function as oncogenes in melanoma cell lines and the silencing of CNTFR reduced macrophage recruitment and M2 polarization.Conclusion: In this study, we have first presented a novel prognostic CIAI model applied to assess immune checkpoint therapy and the efficacy of conventional chemotherapy agents in melanoma patients. Thus providing a new insight for combating melanoma.

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Section: Discussionmentioning

confidence: 99%

A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma

Zhan

Tan

et al. 2022

Front. Pharmacol.

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“…Siomycin A is a thiazole-based antibiotic, isolated from an endophytic Actinomycin sp, derived from the medicinal plant Acanthopanax senticosus (32), which is effective against several malignancies, such as pancreatic cancer, glioblastoma and melanoma (32)(33)(34)(35). The anticancer role of Siomycin A against various cancer cells is well documented.…”

Section: Discussionmentioning

confidence: 99%

Siomycin A induces reactive oxygen species‑mediated cytotoxicity in ovarian cancer cells

Shao¹,

Zhang²,

Gao³

et al. 2021

Oncol Lett

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Ovarian cancer is one of the leading causes of cancer-related death among women worldwide and accounts for 4% of all cancer cases in female patients. To date, ovarian cancer has the poorest prognosis among all types of gynecological cancer; thus, it is necessary to identify prospective therapeutic options. Previous studies have demonstrated the involvement of reactive oxygen species (ROS) in the cytotoxicity of various anticancer drugs against several types of carcinoma, including ovarian cancer. The present study aimed to investigate the anticancer effects of Siomycin A, a thiopeptide antibiotic, on the ovarian cancer cell lines PA1 and OVCAR3. To determine the viability of these cells following exposure to Siomycin A, the MTT assay was used, and apoptosis was determined by ELISA. In addition, mitochondrial membrane potential was determined by JC1 staining, and cellular ROS levels were assessed by dichlorodihydrofluorescein diacetate staining in the presence and absence of antioxidant NAC. The subsequent levels of antioxidant enzymes and glutathione were also determined following Siomycin A treatment in the two cell lines. A combination study with Siomycin A and cisplatin indicated enhanced efficiency of the drugs on ovarian cancer cell viability. The results of the present study also demonstrated that Siomycin A induced ROS production, inhibited the major antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and intracellular GSH in PA1 and OVCAR3 cells, and inhibited the cell viability with an IC 50 of ~5.0 and 2.5 µM after 72 h respectively compared with the untreated controls. Additionally, the Siomycin A-induced ROS production further targeted apoptotic cell death by impairing the mitochondrial membrane potential and modulating the levels of pro- and antiapoptotic proteins compared with those in the corresponding control groups. The administration of the antioxidant N-acetylcysteine significantly abrogated the cytotoxic effects of Siomycin A. In conclusion, the results of the present study demonstrated the role of ROS in Siomycin A-mediated cytotoxicity in ovarian cancer cells.

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“…Forkhead box protein M1 (FOXM1) was known as a predictive factor for tumor progression, and its expression was relevant to a bad prognosis in numerous cancers, such as prostate carcinoma [5], breast carcinoma [6], hepatic carcinoma [7], renal carcinomas [8], and melanoma [9]. However, the correlation between the FOXM1 expression pattern in different human MIBC tissues and its role in carcinoma development was still unclear.…”

Section: Foxm1 and β-Catenin Are Potential Prognostic Markers In Muscmentioning

confidence: 99%

FOXM1 and β-catenin are potential prognostic markers in muscle-invasive bladder carcinoma

Gui¹,

Song²,

Yin³

et al. 2020

Preprint

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BackgroundForkhead box protein M1 (FOXM1) and β-catenin were confirmed to associate with numerous cancers, which attracted more attention in recent years. Our research investigated the expression of FOXM1 and β-catenin and their effects on prognosis of patients with muscle-invasive bladder cancer (MIBC). MethodsIn this study, FOXM1 and β-catenin expression was detected by immunohistochemistry in a study cohort including 121 MIBC patients. Results The results showed significant correlations of FOXM1 and β-catenin expression with tumor stage, tumor grade, and lymph node metastases in MIBC patients. Univariate analysis showed that patients with high FOXM1 (HR = 2.986; P = 0.011) and low β-catenin (HR = 2.623; P = 0.001) expression levels, advanced tumor stage (HR = 2.325; P = 0.002), advanced tumor grade (HR = 2.790; P < 0.001), tumor size (HR = 2.080; P = 0.020), lymph node metastases (HR = 3.392; P < 0.001), or recurrence status (HR = 2.016; P = 0.011) had a significantly higher risk of worse overall survival (OS). In the multivariate analysis, tumor stage (HR = 2.095; P = 0.009), tumor grade (HR = 1.962; P = 0.019), FOXM1 expression (HR = 2.196; P = 0.017) and lymph node metastases (HR = 2.136; P = 0.015) predicted worse OS. ConclusionTherefore, FOXM1 and β-catenin expression was relevant to MIBC incidence, tumor stage, tumor grade, metastasis, and survival and might be a reliable index to judge the prognosis of patients with MIBC.

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Effects of FOXM1 inhibition and ionizing radiation on melanoma cells

Cited by 3 publications

References 28 publications

A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma

A combined aging and immune prognostic signature predict prognosis and responsiveness to immunotherapy in melanoma

Siomycin A induces reactive oxygen species‑mediated cytotoxicity in ovarian cancer cells

FOXM1 and β-catenin are potential prognostic markers in muscle-invasive bladder carcinoma

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