Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R

Gravells, Polly; Hoh, L.; Cánovas, David; Rennie, I G; Sisley, Karen; Bryant, Helen E.

doi:10.1038/bjc.2011.56

Cited by 6 publications

(12 citation statements)

References 25 publications

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“…Glucose uptake and the rate of glycolysis were measured by determining the uptake of 2‐[3H] deoxyglucose by cells and the conversion of 5‐[3H] glucose to 3H 2 O, respectively, as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Glucose uptake and the rate of glycolysis were measured by determining the uptake of 2-[3H] deoxyglucose by cells and the conversion of 5-[3H] glucose to 3H 2 O, respectively, as described previously. (11)(12)(13)(14) Measurement of lactate production. Lactate levels in the culture media of cells were determined by using a Lactate Assay Kit (Biovision, Mountain View, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

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Therapeutic role of EF24 targeting glucose transporter 1‐mediated metabolism and metastasis in ovarian cancer cells

et al. 2013

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Cancer cells require glucose to support their rapid growth through a process known as aerobic glycolysis, or the Warburg effect. As in ovarian cancer cells, increased metabolic activity and glucose concentration has been linked to aggressiveness of cancer. However, it is unclear as to whether targeting the glycolytic pathway may kill the malignant cells and likely have broad therapeutic implications against ovarian cancer metastasis. In the present research, we found that EF24, a HIF-1a inhibitor, could significantly block glucose uptake, the rate of glycolysis, and lactate production compared with vehicle treatment in SKOV-3, A2780 and OVCAR-3 cells. These results might possibly contribute to the further observation that EF24 could inhibit ovarian cancer cell migration and invasion from wound healing and Transwell assays. Furthermore, as an important mediator of glucose metabolism, glucose transporter 1 (Glut1) was found to contribute to the function of EF24 in both energy metabolism and metastasis. To examine the effect of EF24 and the mediated role of Glut1 in vivo in a xenograph subcutaneous tumor model, intraperitoneal metastasis and lung metastasis model were introduced. Our results indicated that EF24 treatment could inhibit tumor growth, intraperitoneal metastasis and lung metastasis of SKOV-3 cells, and Glut1 is a possible mediator for the role of EF24. In conclusion, our results highlight that an anti-cancer reagent with an inhibiting effect on energy metabolism could inhibit metastasis, and EF24 is a possible candidate for anti-metastasis therapeutic applications for ovarian cancer. (Cancer Sci 2013; 104: 1690-1696

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Therapeutic role of EF24 targeting glucose transporter 1‐mediated metabolism and metastasis in ovarian cancer cells

et al. 2013

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“…Treatment of uveal (intraocular) melanoma is aimed to prolonging life and, if possible, conserving the eye and functional vision. The present treatment methods for primary melanoma include enucleation, local resection, radiation therapy, laser hyperthermia, and chemotherapy [9]. Despite successful treatment of a primary intraocular tumor, ∼ 50% of these patients will develop metastases within 10-15 years.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of tumor growth by β-elemene through downregulation of the expression of uPA, uPAR, MMP-2, and MMP-9 in a murine intraocular melanoma model

Hong

Liu

et al. 2015

Melanoma Research

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This paper explores the underlying mechanism through which β-elemene inhibits the growth of intraocular melanoma in a mouse model. C57BL/6J mice were administered a subretinal injection of B16F10 melanoma cells and divided into two groups: treatment and control. The treatment group was administered β-elemene through an intravitreal injection and the control group was injected with a blank emulsion. After 21 days of continuous treatment, tumor masses were removed and weighed. The mRNA expression levels of the urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), matrix metalloproteinase (MMP)-2, and MMP-9 were assayed by real-time PCR, and the protein expression levels of uPA, uPAR, MMP-2, and MMP-9 were assayed by immunocytochemistry and western blotting. Tumor size was inhibited by β-elemene in the treatment group, and the expressions of uPA, uPAR, MMP-2, and MMP-9 were all downregulated at both the mRNA and the protein level compared with the control group. In a mouse model of intraocular melanoma, β-elemene inhibits tumor growth by downregulating the expression of uPA, uPAR, MMP-2, and MMP-9.

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“…MMC prevents DNA replication by forming cross-links in DNA and is valuable as a treatment for a range of solid tumours, including conjunctival melanoma [19,20]. The single agent use of MMC is not however effective for most UM, possibly as previously shown, due to the deficient cytochrome-P450-mediated drug metabolism [21].…”

Section: Introductionmentioning

confidence: 99%

Increased Non-Homologous End Joining Makes DNA-PK a Promising Target for Therapeutic Intervention in Uveal Melanoma

Doherty¹,

Bryant²,

Valluru³

et al. 2019

Cancers

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Uveal melanoma (UM) is the most common primary intraocular tumour in adults, with a mean survival of six months following metastasis. The survival rates have not improved in over 30 years. This study has shown that sister chromatid exchange (SCE) is low in UM which is likely due to a reduced expression of FANCD2. As FANCD2 can function to suppress non-homologous end joining (NHEJ), this study therefore investigated NHEJ in UM. The activation of the catalytic subunit of the NHEJ pathway protein DNA-dependent protein kinase (DNA-PK) was measured by analysing the foci formation and the ligation efficiency by NHEJ determined using a plasmid-based end-joining assay. Using small-interfering RNA (siRNA) knock-down, and chemical inhibitors of DNA-PK, the survival of primary UM cultures and two cell lines were determined. To assess the homologous recombination capacity in response to the inhibition of DNA-PK, a SCE analysis was performed. In addition, to support the findings, the messenger RNA (mRNA) expression of genes associated with NHEJ was analysed using the Cancer Genome Atlas (TCGA)-UM RNAseq data (n = 79). The NHEJ activity and DNA-PKcs activation was upregulated in UM and the inhibition of DNA-PK selectively induced apoptosis and sensitized to ionising radiation and inter-strand cross-linking agents. The inhibition of the NHEJ protein DNA-PK is lethal to UM, indicating a potentially effective therapeutic option, either alone or as a sensitizer for other treatments.

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Resistance of uveal melanoma to the interstrand cross-linking agent mitomycin C is associated with reduced expression of CYP450R

Cited by 6 publications

References 25 publications

Therapeutic role of EF24 targeting glucose transporter 1‐mediated metabolism and metastasis in ovarian cancer cells

Therapeutic role of EF24 targeting glucose transporter 1‐mediated metabolism and metastasis in ovarian cancer cells

Inhibition of tumor growth by β-elemene through downregulation of the expression of uPA, uPAR, MMP-2, and MMP-9 in a murine intraocular melanoma model

Increased Non-Homologous End Joining Makes DNA-PK a Promising Target for Therapeutic Intervention in Uveal Melanoma

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