Relationship of p21 (waf1/cip1) and differentiation in chondrosarcoma cells

Hiraoka, Koji; Zenmyo, Michihisa; Komiya, Setsuro; Kawabata, Rikimaru; Yokouchi, Masahiro; Suzuki, Ryoko; Hamada, Tetsuya; Kato, Seiya; Nagata, Kensei

doi:10.1007/s004280100495

Cited by 16 publications

(15 citation statements)

References 22 publications

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“…Waf1/Cip1 expression related to the differentiation of chondrosarcoma is exclusively found in well-differentiated chondrosarcoma cells (32), and that the up-regulation of p21…”

Section: Discussionmentioning

confidence: 99%

The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells

Sakimura

Tanaka

Yamamoto

et al. 2007

Clinical Cancer Research

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Purpose: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas. Experimental Design: We examined the effects of a HDAC inhibitor, depsipeptide, on the growth of chondrosarcoma cell lines.We also investigated the modulation of the expression levels of extracellular matrix genes and the induction of phenotypic change in chondrosarcoma cells treated with depsipeptide. Finally, we examined the antitumor effect of depsipeptide on chondrosarcoma in vivo. Results: Depsipeptide inhibited the growth of chondrosarcoma cells by inducing cell cycle arrest and/or apoptosis. HDAC inhibitors increased the expression of the a1 chain of type II collagen (COL2A1) gene due to the enhanced histone acetylation in the promoter and enhancer. Depsipeptide also up-regulated the expressions of aggrecan and the a2 chain of type XI collagen (COL11A2) mRNA in a dose-dependent manner. Moreover, long-term treatment with a low dose of depsipeptide resulted in the induction of differentiation into hypertrophic phenotype, as shown by the increment of the a1 chain of type X collagen (COL10A1) expression in chondrosarcoma cells. In vivo studies and histologic analyses confirmed that depsipeptide significantly inhibited tumor growth and induced differentiation into the hypertrophic and mineralized state in chondrosarcoma cells. Conclusions:These results strongly suggest that HDAC inhibitors may be promising reagents for use as a differentiating chemotherapy against chondrosarcomas.Chondrosarcomas represent the second most prevalent primary skeletal malignancy. Because chondrosarcomas are highly resistant to conventional chemotherapy and radiotherapy, surgery is the only effective form of treatment. To date, no effective adjuvant therapy exists for inoperable chondrosarcomas (1, 2). Thus, a novel approach to therapeutic strategy is a priority for improving the prognosis as related to local recurrence, metastasis, and survival.A recent study has shown that the cartilaginous cells of the growth plate during their different states of differentiation and the distinct histologic chondrosarcoma subtypes show striking histologic similarities (3). The normal growth plate represents the chondrocytic maturation process including resting, proliferative, prehypertrophic, and hypertrophic chondrocytes. As a final step, the cartilage matrix becomes mineralized and hypertrophic cells undergo apoptosis. The process is accompanied by the sequential gene expression pattern of the characteristic extracellular matrix. After commitment to the chondrocyte lineage, mesenchymal cells undergo condensation, cease to express type I collagen (COL1), and then differentiate into a chondrocytic phenotype characterized by the expression of type II, IX, and XI...

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“…Waf1/Cip1 expression related to the differentiation of chondrosarcoma is exclusively found in well-differentiated chondrosarcoma cells (32), and that the up-regulation of p21…”

Section: Discussionmentioning

confidence: 99%

The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells

Sakimura

Tanaka

Yamamoto

et al. 2007

Clinical Cancer Research

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“…p21 Waf1/Cip1 plays a critical role in the negative control of cell growth and is generally upregulated in cell arrest either by cell contact, serum deprivation, differentiation or senescence [4] . The human p21 gene consists of 3 exons (68,450 and 1600 bp) but the first exon is not translated. The human p21 protein is 164 amino acids with a molecular mass of 21 kDa and has been conserved during evolution [19] .…”

Section: Structure and Protein Interactions Of P21mentioning

confidence: 99%

“…p21 expression promotes differentiation in megakaryoblast leukemia cell line (CMK) [65] , in megakaryocytes cells (CD34 + ) [66] , in myelomonocytic cell line (U937) [67] , in chondrosarcoma cells (SW1353) [68] , in dendritic cells and macrophages from human peripheral blood monocytes [69] , in skeletal muscles [70] , in mice lungs [70] , in peripheral nervous system neurons in response to nerve growth factor mediated by p300 protein [57] , in myotube differentiation from myoblasts under the influence of the transcription factor MyoD [63] and in laryngeal tumours [71] . Interestingly, p21 was also shown to inhibit differentiation in terminally differentiated of mouse keratinocytes [72] but not those of humans [15] and decrease differentiation in human colon cancer cell line HT29 [73] .…”

Section: P21 and Differentiationmentioning

confidence: 99%

The Biology of p21Waf1/Cip1 - Review Paper

Blundell¹

2006

American J. of Biochemistry and Biotechnology

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p21WAF1/Cip1 belongs to the Cip/Kip family of cyclin kinase inhibitors (CKI) (p21 Waf1/Cip1 , p27Kip1 , p57 Kip1 ). p21 Waf1/Cip1 was first described as a potent and universal inhibitor of cyclin-dependent kinases (Cdks). Two forms of functionally active p21 has been localized and described: a nuclear and a cytoplasmic forms. In this paper the structures of p21 has been described and as well as it functional biology in terms of differentiation, proliferation and apoptotic activities. The upregulation of p21 by p53-dependent and p53-independent mechanisms is also described.

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“…Cell viability was determined by the MTT assay as described previously (19). In brief, LM8 cells were plated in 96-well culture plates at an initial density of 5x10 3 cells/well.…”

Section: Cellsmentioning

confidence: 99%

Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of osteosarcoma

Kawasoe

Yokouchi²,

Ueno³

et al. 2009

Oncol Rep

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Abstract. Although hyperbaric oxygen has been shown to enhance the efficacy of radiotherapy and chemotherapy for the treatment of several malignant tumors, the impact of hyperbaric oxygen on osteosarcoma has not yet been demonstrated. In this study, we investigated the efficacy of hyperbaric oxygen alone and in combination with an anticancer drug as an adjuvant to chemotherapy. In vitro, highly metastatic murine osteosarcoma cell lines were exposed to hyperbaric oxygen and cell viability was examined. Hyperbaric oxygen alone significantly suppressed cell proliferation, and hyperbaric oxygen plus carboplatin exhibited significant synergism in suppression of cell proliferation. In vivo, C3H mice were subcutaneously inoculated with osteosarcoma cells and divided into four groups: control, hyperbaric oxygen, carboplatin, and carboplatin plus hyperbaric oxygen. After 5 weeks, increase in both tumor volume and number of lung metastases was significantly suppressed in the hyperbaric oxygen group. Concomitant hyperbaric oxygen clearly enhanced the chemotherapeutic effects of carboplatin on both tumor growth and lung metastasis in osteosarcoma-bearing mice. Moreover, mortality in the carboplatin plus hyperbaric oxygen group was significantly lower than in the other three groups. These findings suggest that hyperbaric oxygen plus carboplatin combination therapy could be an appropriate therapeutic regimen for the treatment of patients with osteosarcoma.

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Relationship of p21 (waf1/cip1) and differentiation in chondrosarcoma cells

Cited by 16 publications

References 22 publications

The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells

The Effects of Histone Deacetylase Inhibitors on the Induction of Differentiation in Chondrosarcoma Cells

The Biology of p21Waf1/Cip1 - Review Paper

Hyperbaric oxygen as a chemotherapy adjuvant in the treatment of osteosarcoma

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