Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma cells by platinum complexes, the role of ROS-mediated signaling pathways

Xie, Qiang; Lan, Guoqiang; Zhou, Yangliang; Huang, Jiamin; Liang, Yuanwei; Zheng, Wenjie; Fu, Xin; Fan, Cundong; Chen, Tianfeng

doi:10.1016/j.canlet.2014.07.046

Cited by 36 publications

(27 citation statements)

References 41 publications

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“…30 This study verified Tf-NGO@Pt-action modes by flow cytometry. Figures 6 and S4 show that Pt complexes and Tf-NGO@Pt induced large-scale apoptosis in MCF7 cells (see the sub-G 1 populations in the graphs).…”

supporting

confidence: 64%

“…30 NGOs were prepared according to a slightly modified Hummer protocol with modification. [25][26][27][28] For synthesis of the NGO nanosystem, the Pt-complex solution (1 mg/mL) was dropped in 10 mL NGO solution (1 mg/mL) and ultrasound treated for 15 minutes.…”

Section: Materials and Methods Synthesis Of Pt Complex And Preparatiomentioning

confidence: 99%

“…Pt content was determined as previously described by inductively coupled plasma atomic emission spectroscopy (ICP-AES). 12,29,30 cell lines and cell culture…”

Section: Tf Conjugation and Characterizationmentioning

confidence: 99%

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Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy

Zhu¹,

Zhou²,

Chan³

et al. 2017

IJN

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Rational design and construction of delivery nanosystems for anticancer metal complexes is a crucial strategy to improve solubility under physiological conditions and permeability and retention behavior in tumor cells. Therefore, in this study, we designed and synthesize a transferrin (Tf)-conjugated nanographene oxide (NGO) nanosystem as a cancer-targeted nanocarrier of Pt complexes (Tf-NGO@Pt). This nanodelivery system exhibited good solubility under physiological conditions. Moreover, Tf-NGO@Pt showed higher anticancer efficacy against MCF human breast cancer cells than the free Pt complex, and effectively inhibited cancer-cell migration and invasion, with involvement of reactive oxygen species overproduction. In addition, nanolization also enhanced the penetration ability and inhibitory effect of the Pt complex toward MCF7 breast cancer-cell tumor spheroids. The enhancement of anticancer efficacy was positively correlated with increased cellular uptake and cellular drug retention. This study provides a new strategy to facilitate the future application of metal complexes in cancer therapy.

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supporting

confidence: 64%

Section: Materials and Methods Synthesis Of Pt Complex And Preparatiomentioning

confidence: 99%

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Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy

Zhu¹,

Zhou²,

Chan³

et al. 2017

IJN

Self Cite

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“…In the present work, miR-17-5p downregulated the expression of p21, p-p53 (phosphorylated at S15, S46, and S392), TNF RI, and FADD, which might play roles in the radiosensitivity of irradiated tumor cells. Xie et al reported that the phosphorylation of p53 could result in increased radiosensitivity and the inhibition of tumor reproduction [26]. Strigari et al also demonstrated that p53-dependent signals might be responsible for the abscopal effect in RT to sterilize nonirradiated tumor cells through a proapoptotic pathway [27].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

Liu

2016

Oncotarget

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Betel nut chewing is associated with oral cavity cancer. Radiotherapy is one of the therapeutic approaches. Here, we used miR-17-5p antisense oligonucleotides (AS-ODNs) and human apoptosis protein array to clarify which apoptosis-related proteins are increased or decreased by miR-17-5p in betel nut chewing- oral squamous cell carcinoma OC3 cells. Furthermore, miR-17-5p AS-ODN was used to evaluate the radio-sensitization effects both in vitro and in vivo. An OC3 xenograft tumor model in severe combined immunodeficiency mice was used to determine the effect of miR-17-5p AS ODN on tumor irradiation. We simultaneously detected the relative expressions of 35 apoptosis-related proteins in irradiated OC3 cells that were treated with miR-17-5p AS-ODN or a control ODN. Several proteins, including p21, p53, TNF RI, FADD, cIAP-1, HIF-1α, and TRAIL R1, were found to be up- or downregulated by miR-17-5p in OC3 cells; their expression patterns were also confirmed by Western blotting. We further clarified the role of p53 in irradiated OC3 cells, using a p53 overexpression strategy. The results revealed that the enhancement of p53 expression significantly enhanced radiation-induced G2/M arrest of the OC3 cells. In the in vivo study, treatment of miR-17-5p AS-ODN before irradiation significantly enhanced p53 expression and reduced tumor growth. These results suggest that miR-17-5p increases or decreases apoptosis-related proteins in irradiated OC3 cells; its effect on p53 protein expression contributes to the modulation of the radiosensitivity of the OC3 cells.

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“…Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC), typically with low toxicity to surrounding normal tissues (1). Cancer cells resist radiation-induced damage by launching a series of effector, sensors and activating certain stress proteins to repair the damage and escape apoptosis (2).…”

Section: Introductionmentioning

confidence: 99%

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

et al. 2016

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We reported in an earlier study that using mass spectrometry and bioinformatic analysis demonstrated Rac1 protein might be mostly mitochondrial target in the radiosensitization process of nasopharyngeal carcinoma CNE-1 cells. The goal of our current study was to reveal the relationship between Rac1/NADPH pathway and radiosensitization in CNE-1 cells using Rac1 activator, phorbol 12-myristate 13-acetate (PMA) and Rac1 inhibitor NSC23766. The Rac1-GTP expression was determined using a pulldown assay, the Rac1 location using a immunofluorescence with a laser scanning confocal microscope, the NADPH oxidase activity with NBT assay and the reactive oxygen species with DCFH-DA probe. The apoptosis rate was analyzed by flow cytometry, and the expressions of p67(phox) and NFκB-p105/p50 were analyzed by Western blot. After treatment with PMA and 2 Gy radiation (compared to the control), Rac1-GTP was activated and translocated to the cell membrane. NADPH oxidase activity, reactive oxygen species of intracellular concentration and the apoptosis rate increased significantly. The expression of p67(phox) and NFκB-p50 protein also increased. However, in the cells treated with NSC23766 alone or NSC23766 combined with 2 Gy irradiation, the results were just the opposite. Overall, these results indicate that the Rac1 protein may be the key target involved in the radiosensitization of nasopharyngeal carcinoma cells. The activated Rac1/NADPH pathway combined with radiation can increase the radiosensitivity of nasopharyngeal carcinoma cells, and the Rac1/NADPH pathway may be the signaling pathway involved in the radiosensitization process.

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Strategy to enhance the anticancer efficacy of X-ray radiotherapy in melanoma cells by platinum complexes, the role of ROS-mediated signaling pathways

Cited by 36 publications

References 41 publications

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy

Transferrin-functionalized nanographene oxide for delivery of platinum complexes to enhance cancer-cell selectivity and apoptosis-inducing efficacy

MicroRNA-17-5p regulated apoptosis-related protein expression and radiosensitivity in oral squamous cell carcinoma caused by betel nut chewing

The Enhancement of Radiation Sensitivity in Nasopharyngeal Carcinoma Cells via Activation of the Rac1/NADPH Signaling Pathway

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