Modulation of cell cycle control by vitamin D3 and its analogue, EB1089, in human breast cancer cells

Wu, Gengfei; Fan, Robert S.; Li, Wenhui; Ko, Tien C.; Brattain, Michael G.

doi:10.1038/sj.onc.1201329

Cited by 96 publications

(75 citation statements)

References 44 publications

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“…However, the mechanisms by which these compounds generate inhibition of proliferation and induction of apoptosis in tumor cells are not fully understood. The inhibition of cell proliferation mediated by VD3 compounds has been reported to be due to modulation of cell cycle regulators and a G1 phase arrest through induction of p21 and p27 in pancreatic and breast cancer cells (Kawa et al, 1997;Wu et al, 1997;Verlinden et al, 1998). However, another report showed that VD3-induced G1 arrest is associated with a significant decrease of p21 and increase of p27 in squamous cell carcinoma cells (Hershberger et al, 1999).…”

Section: Introductionmentioning

confidence: 97%

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Ling

Huang

et al. 2004

Oncogene

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Although both the antiapoptotic function of survivin and vitamin D 3 (VD3)-mediated cell growth inhibition and apoptosis have been extensively studied, it is not known whether survivin plays a role in VD3 compound-mediated cell growth inhibition and apoptosis induction. Using an isogenic model of MCF-7 breast adenocarcinoma cells (MCF-7E and MCF-7L sublines that are sensitive and resistant to VD3 compounds), we found that VD3 compounds effectively downregulated survivin in VD3-sensitive MCF-7E cells, which was associated with VD3-induced apoptosis. In contrast, VD3 compounds failed to downregulate survivin in VD3-resistant MCF-7L cells, which showed resistant to VD3-induced apoptosis. However, inhibition of survivin expression by small interfering RNA (siRNA) induced cell death per se and further sensitized VD3-induced apoptosis in MCF-7L cells, indicating that the inability of these cells to respond to VD3 is due to the failure to downregulate survivin. Forced expression of survivin not only blocked VD3-mediated G1 cell accumulation but also increased S and G2/M cell populations. VD3 treatment rapidly triggered the activation of p38 MAPK signaling in MCF-7E cells but not in MCF-7L cells. Moreover, inhibition of p38 activation diminished VD3-mediated survivin inhibition and partially rescued VD3-induced cell death. We further showed that VD3 increased the expression of TGFb1 and TGFb receptor 2, and that blocking the function of TGFb receptor 2 diminished VD3 compound-mediated survivin downregulation. Thus, we propose that the VD3 compound-induced growth inhibition and apoptosis induction are at least partially dependent on survivin downregulation via VD3-induced TGFb signaling and the activation of p38 MAPK pathway. Targeting survivin through these pathways may lead to novel applications for cancer therapeutics.

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Section: Introductionmentioning

confidence: 97%

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Ling

Huang

et al. 2004

Oncogene

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“…Increases in p21 expression at the mRNA and protein level have been documented in association with G1 arrest mediated by 1,25(OH) 2 D 3 or certain of its synthetic analogues (James et al 1996, Mørk Hansen et al 2001b. A study in MCF-7 breast cancer cells treated with the vitamin D analogue EB1089 demonstrated a correlation between increased p21 WAF-1/CIP1 protein levels, inhibition of Cdk2-associated histone H1 kinase activity and G1 arrest (Wu et al 1997). Effects of 1,25(OH) 2 D 3 on p27 kip1 appear to vary with cell type.…”

Section: Mechanisms Associated With Inhibitory Effects Of Vitamin D Cmentioning

confidence: 99%

“…Treatment of oestrogen receptor-positive MCF-7 breast cancer cells with 1,25(OH) 2 D 3 induces cell cycle arrest in G0/G1 (Simboli-Campbell et al 1997, Wu et al 1997. These effects are accompanied by alterations in the expression of important cell cycle regulators such as increases in cyclin-dependent kinase (cdk) inhibitors and dephosphorylation of the retinoblastoma protein (Fan & Yu 1995, Mørk Hansen et al 2001b.…”

Section: Mechanisms Associated With Inhibitory Effects Of Vitamin D Cmentioning

confidence: 99%

Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

Colston

Hansen²

2002

Endocrine-Related Cancer

223

180

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It is now well established that, in addition to its central role in the maintenance of extracellular calcium levels and bone mineralization, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), the active form of vitamin D, also acts as a modulator of cell growth and differentiation in a number of cell types, including breast cancer cells. The anti-proliferative effects of 1,25(OH) 2 D 3 have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21WAF-1/CIP1 and p27 kip1 , cyclins and retinoblastoma protein as well as induction of apoptosis. Such studies have led to interest in the potential use of 1,25(OH) 2 D 3 in the treatment or prevention of certain cancers. Since this approach is limited by the tendency of 1,25(OH) 2 D 3 to cause hypercalcaemia, synthetic vitamin D analogues have been developed which display separation of the growth regulating effects from calcium mobilizing actions. This review examines mechanisms by which 1,25(OH) 2 D 3 and its active analogues exert both anti-proliferative and pro-apoptotic effects and describes some of the synthetic analogues that have been shown to be of particular interest in relation to breast cancer.

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“…1,25-D3 is responsible for VDR-mediated apoptosis and inhibits angiogenesis and differentiation in a variety of cancer types (13,(16)(17)(18)(19)(20). 1,25-D3 is a potential antitumor agent because of its ability to regulate cancer cell growth.…”

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confidence: 99%

“…1,25-D3 is well known for its antiproliferative roles including the induction of G 0 -G 1 cell-cycle arrest with associated down-regulation of oncogenic cyclins D1 and D3 and p27/p21 induction (12)(13)(14)(15). 1,25-D3 is responsible for VDR-mediated apoptosis and inhibits angiogenesis and differentiation in a variety of cancer types (13,(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer Cells In Vitro

Kuittinen

Rovio

Staff

et al. 2017

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Abstract. Background/Aim: Endometrial cancer cells areknown to be sensitive to carboplatin and paclitaxel. Furthermore, vitamin D (1, Endometrial cancer is the most common gynecological malignancy in developed countries. In Finland incidence is 13.9 per 100,000 persons a year (1). Most women are diagnosed with early-stage disease and have a high cure rate with surgery alone with a reported 5-year survival rate of 90% (2). Still up to 25% of women will have advanced, high grade or recurrent disease and require additional treatment. In these cases, the therapeutic response to cytotoxic and hormonal agents has been typically only partial and of short duration. There is no generally accepted standard chemotherapy in treatment of advanced and recurrent endometrial carcinoma but simultaneous administration of carboplatin and paclitaxel or carboplatin and pegylated liposomal doxorubicin are widely used (3-8).Vitamin D is an antiproliferative and immunomodulatory secosteroid hormone with a well-established role in maintenance of calcium synthesis. Active metabolite of vitamin D, 1alpha,25-dihydroxyvitamin D 3 (1,25-D3) binds to the vitamin D receptor (VDR) in the cell nucleus. The function and/or expression of the VDR is needed for the 6575 This Αrticle is freely accessible online.Correspondence to:

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Modulation of cell cycle control by vitamin D3 and its analogue, EB1089, in human breast cancer cells

Cited by 96 publications

References 44 publications

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Differential regulation of survivin expression and apoptosis by vitamin D3 compounds in two isogenic MCF-7 breast cancer cell sublines

Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Endometrial Cancer Cells In Vitro

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