In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression

Takahashi, Hiroyuki; Parsons, Peter G.

doi:10.1111/j.1600-0749.1990.tb00294.x

Cited by 34 publications

(28 citation statements)

References 32 publications

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“…Star-shaped cells appeared in cultures treated with 3 mM VPA. Takahashi et al studied the impact of another two HDACis on differentiation in human melanoma cells: sodium butyrate (NaB) and DMSO [47]. They showed that NaB caused the formation of star-shaped cells, whereas DMSO did not affect the cell morphology.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Chodurek

Orchel

et al. 2012

Cellular and Molecular Biology Letters

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Malignant melanoma (melanoma malignum) is one of the most dangerous types of tumor. It is very difficult to cure. In recent years, a lot of attention has been given to chemoprevention. This method uses natural and synthetic compounds to interfere with and inhibit the process of carcinogenesis. In this study, a new treatment strategy was proposed consisting of a combination of 5,7-dimethoxycoumarin (DMC), an activator of melanogenesis, and valproic acid (VPA), a well-known drug that is one of the histone deacetylase inhibitors (HDACis). In conjunction with 1 mM VPA, all of the tested concentrations of DMC (10–150 μM) significantly decreased the proliferation of A-375 cells. VPA and DMC also induced the synthesis of melanin and the formation of dendrite and star-shaped cells. Tyrosinase gene expression and tyrosinase activity significantly increased in response to VPA treatment. Pyrolysis with gas chromatography and mass spectrometry (Py-GC/MS) was used to investigate the structure of the isolated melanin. This showed that the quantitative and qualitative components of melanin degradation products are dependent on the type of applied melanogenesis inductor. Products derived from eumelanin were detected in the pyrolytic profile of melanin isolated from A-375 cells stimulated with DMC. Thermal degradation of melanin isolated from melanoma cells after exposure to VPA or a mixture of VPA and DMC revealed the additional presence of products derived from pheomelanin.

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Section: Discussionmentioning

confidence: 99%

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Chodurek

Orchel

et al. 2012

Cellular and Molecular Biology Letters

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“…After transfer of proteins onto nitrocellulose membrane, immunostaining was carried out as described elsewhere [19]. In order to assess the potential of SCF and c-KIT as differentiation markers for melanocytes, human melanoma cells (MM96E and MM138) were cultured in the presence of sodium butyrate (1.5 raM) or HMBA (10 raM), since these doses were the most effective for induction of various phenotypic alterations in these cell lines with minimal cellular damage [18,20]. After incubation with each drug for 48 h, cells were harvested with trypsin, washed in PBS (pH 7.2), and subjected to Western blot analysis.…”

Section: Methodsmentioning

confidence: 99%

“…The aim of the present study was therefore to compare the l.ocalisation of SCF in normal skin, melanocytic naevi, and malignant melanomas and compare it with the distribution of its receptor, c-KIT. In addition, sodium butyrate and hexamethylene bisacetamide (HMBA), which have been reported to induce various phenotypic alterations in melanoma cells [18,20], were applied to cultured human melanoma cells, to determine whether SCF and/or c-KIT could serve as markers for differentiation of pigment cells.…”

Section: Introductionmentioning

confidence: 99%

Immunohistochemical localisation of stem cell factor (SCF) with comparison of its receptor c-Kit proto-oncogene product (c-KIT) in melanocytic tumours

Takahashi

Kishi

et al. 1995

Vichows Archiv A Pathol Anat

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In order to characterise the distribution and role of stem cell factor (SCF), a recently-reported growth factor for normal melanocytes, we carried out an immunohistochemical study on benign and malignant melanocytic tumours with a comparison with the presence of its receptor c-Kit proto-oncogene product (c-KIT). In normal skin, SCF was mainly observed in endothelial cells of blood vessels but not frequently in basal melanocytes, whereas c-KIT was predominantly localised in tissue mast cells. In benign neoplastic melanocytes (common melanocytic naevi), localisation of SCF and c-KIT was complementary: SCF was mostly found in dermal naevus cells while c-KIT was revealed in epidermal naevus cells, although the expression of the latter antigen was not frequent. Malignant melanoma cells showed less frequent expression of these antigens than those in benign lesions. Of five cultured melanoma cell lines, SCF was observed in only one, and c-KIT was not found in any melanoma cells. No quantitative or qualitative alterations assessed by Western blot analysis were induced in the presence of phenotypic modifiers (sodium butyrate and HMBA). Present data suggest that loss of SCF expression in neoplastic melanocytes is commonly associated with malignant transformation of pigment cells rather than loss of its receptor c-KIT.

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“…Butyrate enhances the cellular content of histone HI0 [IS, 33, 341, and it alters the extent of acetylation [33 -391 phosphorylation [33,38] and methylation [38] ofhistones or other chromosomal proteins. Melanoma cell lines like B16 [40-421, treated with butyrate, cease to proliferate rapidly and start to synthetize melanin in a tyrosine-dependent manner [43] but unlike MEL cells the induction of differentiation is reversible upon removal of the inducing agent. We have studied the regulation of the HI0-mRNA accumulation during the various phases of the butyrate treatment of these cells and after releasing them into an butyrate-free medium.…”

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Induction of H1⁰‐gene expression in B16 murine melanoma cells

Rousseau

Khochbin

Gorka

et al. 1992

European Journal of Biochemistry

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Histone H1 accumulation is associated with the terminal stage of differentiation. Unlike other HI histones, it is able to accumulate in the absence of DNA synthesis, however the transcription of its gene is cell-cycle dependent. The regulation of HIo-gene expression has been studied during the induced differentiation of B16 cells and during reversion of the process, which may be achieved when induced cells are released into an inducing-agent-free medium. During the earlier period of induced differentiation, HI0 mRNA showed over-expression when the cells were still proliferating. Then the amount of HI0 mRNA decreased as the cells became arrested in Go-G1. HI0 mRNA half-life measurements and run-on experiments demonstrated that such modulation of the amount of mRNA originated from a transcriptional control of HIo-gene expression. When induced cells reverted to a proliferative undifferentiated state, HI mRNA decreased very rapidly, indicating that an active process was involved in this decay. This behavior differed from that observed in rat liver hepatocytes allowed to proliferate and de-differentiate after partial hepatectomy, or in murine erythroleukemia cells when the inducing agent was removed from the culture.H 1 histones are involved in nucleosome stabilization and in the maintenance of a higher order of structure in chromatin. Their localization in the nucleus, and the existence of several variants in different organisms [I, 21, supports a hypothetical role as a repressor of transcription [3 -51. In-vitro experiments have confirmed that H1 histones are able to repress RNA polymerase I1 [6, 71 and RNA polymerase 111 [8, 91. HI0, one of the HI variants, was first detected in nonproliferative tissues [lo] and was later shown to appear at a terminal stage of differentiation [I 1 -151, or after growth inhibition [16]. It has been proposed that HI0 is associated with condensed chromatin, in agreement with its putative role in the repression of gene expression during the terminal stage of differentiation [17].HlO, unlike other histones, is accumulated in quiescent cells [18], and its synthesis may be uncoupled from that of DNA [18, 191. Nevertheless, like other histone mRNA, HI '-gene transcription is replication dependent in murine eryhtroleukemia (MEL) cells [20], and, moreover, the rate of transcription is enhanced when the cells are induced to differentiate [21-231. The replication-dependent accumulation of H 1 mRNA was also observed in hepatocytes during rat liver regeneration after partial hepatectomy [24], but in this case the protein accumulation appeared in the cells much later than the accumulation of mRNA, i.e. after the arrest of cell proliferation. It appears that H1° expression is under the control of a dual regulation process, the first one of which is related to DNA replication and concerns mostly the transcrip- tion step, the second occurs in the absence of cell proliferation and would affect primarily the translation step.In order to better understand the regulation of H1 during both proliferat...

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In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression

Cited by 34 publications

References 32 publications

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Immunohistochemical localisation of stem cell factor (SCF) with comparison of its receptor c-Kit proto-oncogene product (c-KIT) in melanocytic tumours

Induction of H1⁰‐gene expression in B16 murine melanoma cells

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In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression

Cited by 34 publications

References 32 publications

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Immunohistochemical localisation of stem cell factor (SCF) with comparison of its receptor c-Kit proto-oncogene product (c-KIT) in melanocytic tumours

Induction of H10‐gene expression in B16 murine melanoma cells

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Induction of H1⁰‐gene expression in B16 murine melanoma cells