Thymocyte Apoptosis Induced by Various Compounds Including YO‐2 Is Accompanied by a Change in Chromatin Structure

Enomoto, Riyo; Sugahara, Chiyoko; Tsuda, Yuko; Okada, Yoshio; Lee, Eibai

doi:10.1196/annals.1329.072

Cited by 2 publications

(1 citation statement)

References 12 publications

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“…We studied well-known models of apoptosis in rat thymocytes, such as the apoptosis induced by the glucocorticoid dexamethasone (Dex) [28][29][30] and the cytotoxic drug etoposide (Eto) [31][32][33][34]. Apoptosis was examined using microscopy and flow cytometry.…”

Section: Introductionmentioning

confidence: 99%

Thymocyte K+, Na+ and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis

Yurinskaya¹,

Moshkov²,

Rozanov³

et al. 2005

Cell Physiol Biochem

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The mechanism of apoptotic cell volume decrease was studied in rat thymocytes treated with dexamethasone (Dex) or etoposide (Eto). Cell shrinkage, i.e. dehydration, was quantified by using buoyant density of the thymocytes in a continuous Percoll gradient. The K⁺ and Na⁺ content of cells from different density fractions were assayed by flame emission analysis. Apoptosis was tested by microscopy and flow cytometry of acridine orange stained cells as well as by flow DNA cytometry. Treatment of the thymocytes with 1 µM Dex for 4-5.5 h or 50 µM Eto for 5 h resulted in the appearance of a new distinct high-density cell subpopulation. The cells from this heavy subpopulation but not those with normal buoyant density had typical features of apoptosis. Apoptotic increase of cell density was accompanied by a decrease in cellular K⁺ content, which exceeded the simultaneous increase in cellular Na⁺ content. Cellular loss of K⁺ contributed to most of the estimated loss of cellular osmolytes, but owing to the parallel loss of cell water, the decrease in cytosolic K⁺ concentration was less than one third. Due to gain of Na⁺ and loss of cell water the cytosolic Na⁺ concentration in thymocytes rose following treatment with Dex (5.5 h) or Eto (5 h) by a factor of about 3.6 and 3.1, respectively.

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Section: Introductionmentioning

confidence: 99%

Thymocyte K+, Na+ and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis

Yurinskaya¹,

Moshkov²,

Rozanov³

et al. 2005

Cell Physiol Biochem

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YO2 Induces Melanoma Cell Apoptosis through p53-Mediated LRP1 Downregulation

Salama

Takahashi

Tsuda

et al. 2022

Cancers

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The multifunctional endocytic receptor low-density lipoprotein receptor-related protein 1 (LRP1) has been implicated in melanoma growth. However, the mechanism of LRP1 expression in melanoma cells remains only partially understood. In most melanomas, the TP53 tumor suppressor is retained as a non-mutated, inactive form that fails to suppress tumors. We identify TP53 as a regulator of LRP1-mediated tumor growth. TP53 enhances the expression of miRNA miR-103/107. These miRNAs target LRP1 expression on melanoma cells. TP53 overexpression in human and murine melanoma cells was achieved using lentivirus or treatment with the small molecule YO-2, a plasmin inhibitor known to induce apoptosis in various cancer cell lines. TP53 restoration enhanced the expression of the tumor suppressor miR-103/107, resulting in the downregulation of LRP1 and suppression of tumor growth in vivo and in vitro. Furthermore, LRP1 overexpression or p53 downregulation prevented YO-2-mediated melanoma growth inhibition. We identified YO-2 as a novel p53 inducer in melanoma cells. Cotreatment of YO-2 with doxorubicin blocked tumor growth in vivo and in a murine melanoma model, suggesting that YO-2 exerts anti-melanoma effects alone or in combination with conventional myelosuppressive drugs.

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Thymocyte Apoptosis Induced by Various Compounds Including YO‐2 Is Accompanied by a Change in Chromatin Structure

Cited by 2 publications

References 12 publications

Thymocyte K<sup>+</sup>, Na<sup>+</sup> and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis

Thymocyte K<sup>+</sup>, Na<sup>+</sup> and Water Balance During Dexamethasone- and Etoposide-Induced Apoptosis

YO2 Induces Melanoma Cell Apoptosis through p53-Mediated LRP1 Downregulation

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