Combined Effects of Treatment with Trientine, a Copper-Chelating Agent, and X-Irradiation on Tumor Growth in Transplantation Model of a Murine Fibrosarcoma

Hayashi, Masanobu; Hirai, Ryou; Ishihara, Yuusuke; Horiguchi, Noboru; Endoh, Daiji; Okui, Toyo

doi:10.1292/jvms.69.1039

Cited by 2 publications

(2 citation statements)

References 35 publications

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“…The obtained results indicated that at the doses of 4, 5 and 6 Gy, the X-ray did not cause any death of mice after 20 days post-irradiation; however, the dose of 7 Gy caused some deaths of mice after 7 days post-irradiation. This result was consistent with results reported in previous studies [24,25,26,27]. Based on this, we selected the dose of 6.0 Gy for further experiments.…”

Section: Resultssupporting

confidence: 92%

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

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et al. 2019

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Radiotherapy side-effects present serious problems in cancer treatment. Melanin, a natural polymer with low toxicity, is considered as a potential radio-protector; however, its application as an agent against irradiation during cancer treatment has still received little attention. In this study, nanomelanin particles were prepared, characterized and applied in protecting the spleens of tumor-bearing mice irradiated with X-rays. These nanoparticles had sizes varying in the range of 80–200 nm and contained several important functional groups such as carboxyl (-COO), carbonyl (-C=O) and hydroxyl (-OH) groups on the surfaces. Tumor-bearing mice were treated with nanomelanin at a concentration of 40 mg/kg before irradiating with a single dose of 6.0 Gray of X-ray at a high dose rate (1.0 Gray/min). Impressively, X-ray caused mild splenic fibrosis in 40% of nanomelanin-protected mice, whereas severe fibrosis was observed in 100% of mice treated with X-ray alone. Treatment with nanomelanin also partly rescued the volume and weight of mouse spleens from irradiation through promoting the transcription levels of splenic Interleukin-2 (IL-2) and Tumor Necrosis Factor alpha (TNF-α). More interestingly, splenic T cell and dendritic cell populations were 1.91 and 1.64-fold higher in nanomelanin-treated mice than those in mice which received X-ray alone. Consistently, the percentage of lymphocytes was also significantly greater in blood from nanomelanin-treated mice. In addition, nanomelanin might indirectly induce apoptosis in tumor tissues via activation of TNF-α, Bax, and Caspase-3 genes. In summary, our results demonstrate that nanomelanin protects spleens from X-ray irradiation and consequently enhances immunoactivity in tumor-bearing mice; therefore, we present nanomelanin as a potential protector against damage from radiotherapy in cancer treatment.

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Section: Resultssupporting

confidence: 92%

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Loc

Tri

et al. 2019

Materials

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“…Therefore, induction of apoptosis in the tumor cells by trientine may play role in inhibition of tumor growth, in addition to destroying tumor vasculature. Our study showed that trientine and X-irradiation interact additively in inhibition of tumor growth and induction of cell death in vitro [17]. Induction of apoptosis by trientine may reduce the radiation dose required to suppress tumor growth in radiation therapy, resulting in a decrease in occurrence of deleterious side effects of radiation, and provide clinical benefits for tumor treatments.…”

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confidence: 68%

Trientine, a Copper-Chelating Agent, Induced Apoptosis in Murine Fibrosarcoma Cells by Activation of the p38 MAPK Pathway

et al. 2009

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ABSTRACT. We have reported that treatment with trientine, Cu-chelating agent, inhibits tumor growth in a murine transplantation model using fibrosarcoma and induces apoptosis in tumor cells in vivo and in vitro. When fibrosarcoma cells were treated with 10 mM trientine, the activities of p38 MAPK in treated cells were approximately 3-4 times higher than those in untreated cells. Proportions of cells in which apoptosis was induced by trientine increased in an incubation time-dependent manner from days 2 to 6. The proportions of apoptotic cells in the cells treated with trientine and SB203580, an inhibitor of p38 MAPK, were approximately 50% in those of cells treated with trientine alone. The present results showed that the p38 MAPK pathway may play an important role in induction of apoptosis in fibrosarcoma cells by trientine.

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Combined Effects of Treatment with Trientine, a Copper-Chelating Agent, and X-Irradiation on Tumor Growth in Transplantation Model of a Murine Fibrosarcoma

Cited by 2 publications

References 35 publications

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Nanomelanin Potentially Protects the Spleen from Radiotherapy-Associated Damage and Enhances Immunoactivity in Tumor-Bearing Mice

Trientine, a Copper-Chelating Agent, Induced Apoptosis in Murine Fibrosarcoma Cells by Activation of the p38 MAPK Pathway

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