p53-independent structure-activity relationships of 3-ring mesogenic compounds’ activity as cytotoxic effects against human non-small cell lung cancer lines

Fukushi, S; Yoshino, Hironori; Yoshizawa, Atsushi; Kashiwakura, Ikuo

doi:10.1186/s12885-016-2585-6

Cited by 13 publications

(13 citation statements)

References 48 publications

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“…p53 plays a vital role in the regulation if cell cycle transition, checkpoint activation, and apoptotic machinery in tumor cells, which control expression of p21 and p27 . It has been reported that TRIM59, as an E3 ubiquitin ligases, was able to interacted with p53, increasing its ubiquitination and degradation in gastric cancer cells .…”

Section: Discussionmentioning

confidence: 99%

“…Our results showed that TRIM59 induced paclitaxel resistance with apoptosis inhibition. To find out the underlying mechanism, we examined several related protein and found that TRIM59 downregulated cleaved caspase 3, cleaved caspase 9, cleaved PARP, and cytochrome c release, indicating TRIM59 could reduce the activation p53 plays a vital role in the regulation if cell cycle transition, checkpoint activation, and apoptotic machinery in tumor cells, [21][22][23][24] which control expression of p21 and p27. [25][26][27] It has been reported that TRIM59, as an E3 ubiquitin ligases, was able to interacted with p53, increasing its ubiquitination and degradation in gastric cancer cells.…”

Section: Trim59 Activates Akt Signaling and Promotes P53 Ubiquitinamentioning

confidence: 99%

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TRIM59 overexpression correlates with poor prognosis and contributes to breast cancer progression through AKT signaling pathway

Liu

Dong

Zhao

et al. 2018

Molecular Carcinogenesis

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TRIM59 has been recently implicated in the carcinogenesis of several cancers such as lung cancer, gastric cancer, and bladder cancer. However, its expression pattern and clinical significance has not been investigated in human breast cancer. In the present study, we examined TRIM59 protein expression in 95 cases of breast cancer tissues using immunohistochemistry. We found that TRIM59 was upregulated in 42 out of 95 cases and correlated with TNM stage (P = 0.0056), lymph node metastasis (P = 0.0088) and poor prognosis (P = 0.0092). Importantly, TRIM59 level was higher in triple-negative breast cancer (TNBC) (P = 0.0157). Expression of TRIM59 protein was also upregulated in breast cancer cell lines compared to normal MCF-10A cell line. TRIM59 plasmid and shRNA transfection was performed in MCF-7 and SK-BR-3 cells respectively. TRIM59 overexpression promoted cell proliferation, invasion, migration, cell cycle transition, and paclitaxel resistance, whereas TRIM59 depletion showed the opposite results. Further analysis showed that TRIM59 overexpression upregulated expression of cyclinA, cyclinE, Bcl-xl, Bcl-2, p-AKT, and downregulated expression of p21, p27, p53. AKT inhibitor treatment abolished the effect of TRIM59 on Bcl-2 expression. TRIM59 overexpression also upregulated the level of p53 ubiquitination. In conclusion, TRIM59 overexpression correlates with poor prognosis and promotes malignant behavior through regulation of AKT pathway in human breast cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Trim59 Activates Akt Signaling and Promotes P53 Ubiquitinamentioning

confidence: 99%

TRIM59 overexpression correlates with poor prognosis and contributes to breast cancer progression through AKT signaling pathway

Liu

Dong

Zhao

et al. 2018

Molecular Carcinogenesis

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“…Cell death was analyzed using Annexin V-FITC (BioLegend, Inc., San Diego, CA, USA), PI, and Annexin V binding buffer (BioLegend, Inc.), as reported previously (20). Statistical analysis.…”

Section: Medium Transfer Experimentsmentioning

confidence: 99%

Effects of Nrf2 knockdown on the properties of irradiated cell conditioned medium from A549 human lung cancer cells

et al. 2018

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Abstract. The nuclear factor erythroid 2-related factor 2 (Nrf2) plays an important role in cellular defense against oxidative stress. Recent studies have demonstrated that Nrf2 is a useful target for cancer treatment, including radiation therapy. Ionizing radiation affects, not only the irradiated cells, but also the non-irradiated neighboring cells, and this effect is known as radiation-induced bystander effect. Upon exposure to radiation, the irradiated cells transmit signals to the non-irradiated cells via gap junctions or soluble factors. These signals in turn cause biological effects, such as a decrease in the clonogenic potential and cell death, in the non-irradiated neighboring cells. Nrf2 inhibition enhances cellular radiosensitivity. However, whether this modification of radiosensitivity by Nrf2 inhibition affects the radiation-induced bystander effects is unknown. In this study, we prepared an Nrf2 knockdown human lung cancer cell A549 and investigated whether the effects of irradiated cell conditioned medium (ICCM) on cell growth and cell death induction of non-irradiated cells vary depending on the Nrf2 knockdown. We found that Nrf2 knockdown resulted in a decrease in the cell growth and an increase in the radiosensitivity of A549 cells. When non-irradiated A549 cells were transfected with control siRNA and treated with ICCM, no significant difference was observed in the cell growth and proportion of Annexin V + dead cells between ICCM from non-irradiated cells and that from 2 or 8 Gy-irradiated cells. Similarly, no significant difference was observed in the cell growth and cell death induction upon treatment with ICCM in the Nrf2 knockdown A549 cells. Taken together, these results suggest that Nrf2 knockdown decreases cell growth and enhances the radiosensitivity of A549 cells; however, it does not alter the effect of ICCM on cell growth. IntroductionIonizing radiation causes biological effects, such as cell death and chromosomal aberrations, on cells. There are many evidences that ionizing radiation affects, not only the irradiated cells, but also the non-irradiated neighboring cells (1-3). Such response is known as radiation-induced non-targeted effects, which includes genomic instability and radiation-induced bystander effects. Genomic instability is characterized by effects such as delayed gene mutation and chromosomal aberrations that occur in the progeny of irradiated cells (3). In radiation-induced bystander effects, it has been suggested that the irradiated cells transmit signals to the non-irradiated cells via gap junctions or soluble factors (such as cytokines and growth factors) (1,2). To investigate the soluble factor-mediated bystander effects in vitro, non-irradiated cells were co-cultured with irradiated cells or cultured in irradiated cell conditioned medium (ICCM). It has been reported that non-irradiated cells co-cultured with irradiated cells or treated with ICCM undergo various biological responses, such as DNA double-strand breaks, decrease in clonogenic cell survival, and cell...

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“…Cell death was analyzed using Annexin V-FITC (BioLegend Inc., San Diego, CA, USA), PI, and Annexin V binding buffer (BioLegend Inc.), as reported previously (13). Stained cells were analyzed by performing flow cytometry (Cytomics FC500; Beckman Coulter, Inc., Brea, CA, USA).…”

Section: Sodium Dodecyl Sulfate-polyacrylamide Gel Electrophoresis Anmentioning

confidence: 99%

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

et al. 2018

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Abstract. Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy. However, it is unclear whether ionizing radiation affects the cytotoxicity of RLR agonists against cancer cells. Therefore, in the present study the effects of cotreatment with ionizing radiation and RLR agonists on cytotoxicity against human non-small cell lung cancer cells A549 and H1299 was investigated. Treatment with RLR agonist poly(I:C)/LyoVec™ [poly(I:C)] exerted cytotoxic effects against human non-small cell lung cancer. The cytotoxic effects of poly(I:C) were enhanced by cotreatment with ionizing radiation, and poly(I:C) pretreatment resulted in the radiosensitization of non-small cell lung cancer. Furthermore, cotreatment of A549 and H1299 cells with poly(I:C) and ionizing radiation effectively induced apoptosis in a caspase-dependent manner compared with treatment with poly(I:C) or ionizing radiation alone. These results indicate that RLR agonists and ionizing radiation cotreatment effectively exert cytotoxic effects against human non-small cell lung cancer through caspase-mediated apoptosis.

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p53-independent structure-activity relationships of 3-ring mesogenic compounds’ activity as cytotoxic effects against human non-small cell lung cancer lines

Cited by 13 publications

References 48 publications

TRIM59 overexpression correlates with poor prognosis and contributes to breast cancer progression through AKT signaling pathway

TRIM59 overexpression correlates with poor prognosis and contributes to breast cancer progression through AKT signaling pathway

Effects of Nrf2 knockdown on the properties of irradiated cell conditioned medium from A549 human lung cancer cells

Effects of retinoic acid-inducible gene-I-like receptors activations and ionizing radiation cotreatment on cytotoxicity against human non-small cell lung cancer inï¿½vitro

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