Combination of Melatonin and Zoledronic Acid Suppressed the Giant Cell Tumor of Bone in vitro and in vivo

Melatonin (Mlt) confers potential antitumor effects in various types of cancer. However, to the best of our knowledge, the role of Mlt in the giant cell tumor of bone (GCTB) remains unknown. Moreover, further research is required to assess whether Mlt can enhance the therapeutic effect of zoledronic acid (Zol), a commonly used anti-GCTB drug. In this research, we investigated the effects of Mlt, Zol, and the combination of these two drugs on GCTB cells’ characteristics, including cell proliferation, apoptosis, osteogenic differentiation, migration, and invasion. The cell counting kit-8 (CCK-8) assay, colony formation assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL), alkaline phosphatase (ALP) staining, alizarin red staining (ARS), scratch wound healing assay, and transwell experiment were performed, respectively. Our results showed that Mlt could effectively inhibit the proliferation, migration, and invasion of GCTB cells, as well as promote the apoptosis and osteogenic differentiation of tumor cells. Of note, a stronger antitumor effect was observed when Mlt was combined with Zol treatment. This therapeutic effect might be achieved by inhibiting the activation of both the Hippo and NF-κB pathways. In conclusion, our study suggests that Mlt can be a new treatment for GCTB, which could further enhance the antitumor effect of Zol.

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Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone

Nature Communications ◽

10.1038/s41467-020-18955-y ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Pavlo Lutsik ◽

Annika Baude ◽

Daniela Mancarella ◽

Simin Öz ◽

Alexander Kühn ◽

...

Keyword(s):

Dna Methylation ◽

Osteogenic Differentiation ◽

Giant Cell Tumor ◽

Giant Cell ◽

Stromal Cells ◽

Chromatin Accessibility ◽

Cell Tumor ◽

Epigenetic Alterations ◽

Epigenetic Landscape ◽

Line System

Abstract The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level, that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability, as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W-associated changes.

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Early evaluation of the therapeutic effect of denosumab on tartrate-resistant acid phosphatase 5b expression in a giant cell tumor of bone: a case report

BMC Research Notes ◽

10.1186/1756-0500-7-608 ◽

2014 ◽

Vol 7 (1) ◽

pp. 608 ◽

Cited By ~ 8

Author(s):

Naoto Watanabe ◽

Seiichi Matsumoto ◽

Takashi Shimoji ◽

Keisuke Ae ◽

Taisuke Tanizawa ◽

...

Keyword(s):

Case Report ◽

Acid Phosphatase ◽

Giant Cell Tumor ◽

Giant Cell ◽

Therapeutic Effect ◽

Cell Tumor ◽

Tartrate Resistant Acid Phosphatase ◽

Early Evaluation

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Zoledronic acid-loaded bone cement as a local adjuvant therapy for giant cell tumor of the sacrum after intralesional curettage

European Spine Journal ◽

10.1007/s00586-015-3978-y ◽

2015 ◽

Vol 24 (10) ◽

pp. 2182-2188 ◽

Cited By ~ 10

Author(s):

Kun-Hui Chen ◽

Po-Kuei Wu ◽

Cheng-Fong Chen ◽

Wei-Ming Chen

Keyword(s):

Zoledronic Acid ◽

Adjuvant Therapy ◽

Bone Cement ◽

Giant Cell Tumor ◽

Giant Cell ◽

Cell Tumor ◽

Intralesional Curettage

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Globally altered epigenetic landscape and lagging osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone

10.1101/2020.05.26.20089888 ◽

2020 ◽

Author(s):

Pavlo Lutsik ◽

Annika Baude ◽

Daniela Mancarella ◽

Simin Oez ◽

Alexander Kuehn ◽

...

Keyword(s):

Dna Methylation ◽

Osteogenic Differentiation ◽

Giant Cell Tumor ◽

Giant Cell ◽

Stromal Cells ◽

Chromatin Accessibility ◽

Cell Tumor ◽

Epigenetic Alterations ◽

Epigenetic Landscape ◽

Line System

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W associated changes.

Download Full-text