Tumor Progression Accelerated by Oxygen Species and Its Chemoprevention

Hosokawa, Masuo; Nakai, Kazumoto; Okada, Futoshi

doi:10.1007/978-4-431-67017-9_14

Cited by 4 publications

(5 citation statements)

References 9 publications

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“…Furthermore, spindle misorientation in HeLa cells exposed to ionizing radiation was attenuated by treatment with 2‐OctadecylAA. These data suggest a novel action and mechanism of 2‐OctadecylAA, which was previously evaluated as an antioxidant with anticarcinogenic activities in rodent systems 24–27 and support RhoGDIβ as a new therapeutic or protective target for human carcinogenesis.…”

Section: Introductionsupporting

confidence: 58%

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

Doi

Togari

Minagi

et al. 2021

J of Cellular Biochemistry

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The appropriate regulation of spindle orientation maintains proper tissue homeostasis and avoids aberrant tissue repair or regeneration. Spindle misorientation due to imbalance or improper functioning leads to a loss of tissue integrity and aberrant growth, such as tissue loss or overgrowth. Pharmacological manipulation to prevent spindle misorientation will enable a better understanding of how spindle orientation is involved in physiological and pathological conditions and will provide therapeutic possibilities to treat patients associated with abnormal tissue function caused by spindle misorientation. N‐terminal‐deleted Rho guanine nucleotide dissociation inhibitor β (RhoGDIβ/RhoGDI2/LyGDI) produced by caspase‐3 activation perturbs spindle orientation in surviving cells following exposure to either ionizing radiation or UVC. Thus, presumably, RhoGDIβ cleaved by caspase‐3 activation acts as a determinant of radiation‐induced spindle misorientation that promote aberrant tissue repair due to deregulation of directional organization of cell population and therefore becomes a potential target of drugs to prevent such response. The objective of this study was to screen and identify chemicals that suppress RhoGDIβ expression. We focused our attention on ascorbic acid (AA) derivatives because of their impact on the maintenance of skin tissue homeostasis. Here, we screened for AA derivatives that suppress RhoGDIβ expression in HeLa cells and identified a lipophilic derivative, 2‐O‐octadecylascorbic acid (2‐OctadecylAA), as a novel RhoGDIβ inhibitor that ameliorated ionizing radiation‐induced abnormal spindle orientations. Among all examined AA derivatives, which were also antioxidative, the inhibition activity was specific to 2‐OctadecylAA. Therefore, this activity was not due to simple antioxidant properties. 2‐OctadecylAA was previously shown to prevent hepatocellular carcinoma development. Our findings suggest that the anticarcinogenic effects of 2‐OctadecylAA are partly due to RhoGDIβ inhibition mechanisms by which spindle orientation perturbations are attenuated. Thus, the molecular targeting features of RhoGDIβ warrant its further development for the treatment or control of spindle orientation abnormalities that affect epithelial homeostasis.

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Section: Introductionsupporting

confidence: 58%

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

Doi

Togari

Minagi

et al. 2021

J of Cellular Biochemistry

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“…All of the malignant fibrosarcoma cell lines used in this study, converted from QR-32 cells by inflammation induced at the implantation site, expressed high levels of thymosin-␤4 mRNA. We have recently established an in vivo model of tumor progression in which the QR-32 cells acquire malignant phenotype by administration of antitumor drugs, such as adriamycin, 9 cis-diaminedichloro-platinum (II) (cisplatin), or UFT. 10 Such antitumor drug-induced malignant tumor cell lines express only a slight increase of thymosin-␤4 mRNA expression (less than threefold as compared to QR-32 cells, data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…The tumor progression model of mouse fibrosarcoma cells (QR clone) has been established by our group, which has advantages compared to other models. [5][6][7][8][9][10] The QR tumor clones regress spontaneously after injection of up to 2 ϫ 10 5 cells subcutaneously or 1 ϫ 10 6 cells intravenously in normal syngeneic mice; the tumor regression is mediated by host immunity because the tumor cells grow progressively in immunosuppressed or nude mice and a tumor cell-derived immunosuppressive factor, prostaglandin E 2 (PGE 2 ) is associated with this process. 11 Thus by using QR clones, we are able to mimic the natural course of tumor progression, ie, transition from weak tumorigenicity and nonmetastatic benign tumor cells or dormant state of tumor cells to tumorigenic/metastatic malignant tumor cells in mice.…”

mentioning

confidence: 99%

“…The transitional change can be determined by augmented tumorigenicity or metastatic potential. [5][6][7][8][9][10] The model is available for detection of possible internal or external factors for tumor progression. We have previously identified that inflammation [5][6][7]12 or antitumor drug treatments 8 -10 accelerated tumor progression and the resultant daughter cells possessed irreversibly stable malignant phenotypes, all of which derived from a clonal QR-32 tumor line.…”

mentioning

confidence: 99%

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Thymosin-β4 Regulates Motility and Metastasis of Malignant Mouse Fibrosarcoma Cells

Kobayashi¹,

Okada²,

Fujii³

et al. 2002

The American Journal of Pathology

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117

115

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We identified a thymosin-beta4 gene overexpression in malignant mouse fibrosarcoma cells (QRsP-30) that were derived from clonal weakly tumorigenic and nonmetastatic QR-32 cells by using a differential display method. Thymosin-beta4 is known as a 4.9-kd polypeptide that interacts with G-actin and functions as a major actin-sequestering protein in cells. All of the six malignant fibrosarcoma cell lines that have been independently converted from QR-32 cells expressed high levels of thymosin-beta4 mRNA and its expression in tumor cells was correlated with tumorigenicity and metastatic potential. Up-regulation of thymosin-beta4 in QR-32 cells (32-S) transfected with sense thymosin-beta4 cDNA converted the cells to develop tumors and formed numerous lung metastases in syngeneic C57BL/6 mice. In contrast, antisense thymosin-beta4 cDNA-transfected QRsP-30 (30-AS) cells reduced thymosin-beta4 expression, and significantly lost tumor formation and metastases to distant organs. Vector-alone transfected cells (32-V or 30-V cells) behaved like their parental cells. We observed that tumor cell motility, cell shape, and F-actin organization is regulated in proportion to the level of thymosin-beta4 expression. These findings indicate that thymosin-beta4 molecule regulates fibrosarcoma cell tumorigenicity and metastasis through actin-based cytoskeletal organization.

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“…In our previous study, we demonstrated that expression levels of thymosin-b4 after progressive conversion of murine fibrosarcoma cells differed depending on the cause of progression. We have also established other in vivo models of tumor progression in which the QR32 cells acquire the malignant phenotype by administration of anti-tumor drugs [45,46], and such anti-tumor drug-induced malignant tumor cell lines have only a slight increase of thymosin-b4 mRNA expression (less than 3-fold as compared to QR-32 cells, data not shown). In this way, the tumor cells acquired similar malignant phenotypes via different intracellular signaling pathways in the course of progression.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines

Hayashi

Kuramitsu²,

Okada

et al. 2005

Proteomics

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Tumor development and progression consist of a series of complex processes involving multiple changes in gene expression (Paolo et al. Physiol. Rev., 1993, 73, 161-195; Lance et al. Cell., 1991, 64, 327-336). Tumor cells acquire an invasive and metastatic phenotype that is the main cause of death for cancer patients. Therefore, for early diagnosis and effective therapeutic intervention, we need to detect the alterations associated with transition from benign to malignant tumor cells on a molecular basis. To unravel alterations concerned with tumor progression, the proteomic approach has attracted great attention because it can identify qualitative and quantitative changes in protein composition, including post-translational modifications. In this study, we performed proteomic differential display analysis for the expression of intracellular proteins in the regressive cancer cell line QR-32 and the inflammatory cell-promoting progressive cancer cell line QRsP-11 of murine fibrosarcoma by two-dimensional gel electrophoresis and mass spectrometry using an Agilent 1100 LC/MSD Trap XCT. We found 11 protein spots whose expression was different between QR-32 and QRsP-11 cells and identified nine proteins, seven of which, calreticulin precursor, tropomyosin 1 alpha chain, annexin A5, heat shock protein (HSP)90-alpha, HSP90-beta, PEBP, and Prx II, were over-expressed, and two, Anp32e and HDGF, which were down-regulated. The results suggest an important complementary role for proteomics in identification of molecular abnormalities in tumor progression.

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Tumor Progression Accelerated by Oxygen Species and Its Chemoprevention

Cited by 4 publications

References 9 publications

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

2‐O‐Octadecylascorbic acid represses RhoGDIβ expression and ameliorates DNA damage‐induced abnormal spindle orientations

Thymosin-β4 Regulates Motility and Metastasis of Malignant Mouse Fibrosarcoma Cells

Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines

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