Valproic Acid Induces Notch1 Signaling in Small Cell Lung Cancer Cells

Platta, Christopher S.; Greenblatt, David Yü; Kunnimalaiyaan, Muthusamy; Chen, Herbert

doi:10.1016/j.jss.2008.03.008

Cited by 59 publications

(52 citation statements)

References 29 publications

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“…Th e cells formed of treated with NaVP cells formed smaller tumors as well. Previous studies have shown in vitro eff ect of NaVP on the other SCLC cell line DMS53, when treatment with NaVP concentrations as low as 1 mM signifi cantly impaired the cell mitochondrial activity, while higher concentrations (6 mM -10 mM) of NaVP resulted in the absence of tumor markers [15]. Similar results have been shown testing valproic acid on diff erent tumor cell lines other than SCLC.…”

Section: Discussionsupporting

confidence: 73%

Human small cell lung cancer cell line (NCI-H146) tumor behaviour on the chicken embryo chorioallantoic membrane after the sodium valproate treatment

Šlekienė

Mozūraitė

Vosyliūtė

et al. 2017

PoA

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Small cell lung cancer (SCLC) is an aggressive form of cancer with 5-year survival rate and poor prognosis. Since patients` initial response to therapy is rapidly followed by a relapse with the drug-resistant disease, new therapies are required. The aim was to evaluate whether H146 cell line tumor was able to maintain the morphological pattern when grafted on the chicken embryo chorioallantoic membrane (CAM). Also, to evaluate the morphological changes in the CAM after grafting the tumor without or with treatment with sodium valproate (NaVP). The cell culture of the commercial NCI-H146 cell line was used for the formation of the tumor. The tumor of 1x10 6 cells and I type rat tail collagen was dropped onto the absordable sponge and instantly grafted on CAM. After 5 days of incubation chicken embryos were sacrificed and CAMs were cut out. Standard H&E staining and immunohistochemistry (CD56) were performed. The histomorphometrical analysis of non-treated (n=5), 4 mM NaVP-treated (n=5) and 8 mM (n=5) of NaVPtreated groups was performed. The thickness of the CAM was measured in all the investigated groups in the areas under the onplant and in the neighbouring sites. H146 cells are able to maintain morphological appearance on the CAM and retained the expression of specific profile for CD56. H146 cell tumor increased the thickness of the CAM under the tumor in the nontreated group (509.2±184μm). After treatment with 4 mM and 8 mM of NaVP CAM thickness decreased (362±232.6 μm and 147.8±98.4 μm respectively; p<0.0001). The effect of NaVP on CAM increased with increasing solution

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Section: Discussionsupporting

confidence: 73%

Human small cell lung cancer cell line (NCI-H146) tumor behaviour on the chicken embryo chorioallantoic membrane after the sodium valproate treatment

Šlekienė

Mozūraitė

Vosyliūtė

et al. 2017

PoA

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“…The NOTCH1 signaling pathway is silenced in many neuroendocrine malignancies, including SCLC (40). Activation of NOTCH1 signaling inhibited the growth of SCLC cells (25), and Genomic profiling of SCLC is still in its infancy, delaying the development of molecularly targeted therapies. Our approach to use combination therapy with CBL0137 and cisplatin is an important means to circumvent the development of resistance to standard therapy (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The oncogenic role of NOTCH has been identified in many cancers, including NSCLC (22), T-ALL (23), and GBM (24). In contrast, NOTCH1 signaling is suppressed in neuroendocrine tumor cells, including SCLC (25,26), indicating that inducing its expression is an attractive strategy for treating these tumors.…”

Section: Introductionmentioning

confidence: 99%

The FACT inhibitor CBL0137 Synergizes with Cisplatin in Small-Cell Lung Cancer by Increasing NOTCH1 Expression and Targeting Tumor-Initiating Cells

Lindner

Coleman

et al. 2018

Cancer Research

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Traditional treatments of small cell lung cancer (SCLC) with cisplatin, a standard of care therapy, spare the tumor-initiating cells (TIC) that mediate drug resistance. Here we report a novel therapeutic strategy that preferentially targets TIC in SCLC in which cisplatin is combined with CBL0137, an inhibitor of the histone chaperone facilitates chromatin transcription (FACT), which is highly expressed in TIC. Combination of cisplatin and CBL0137 killed patient-derived and murine SCLC cell lines synergistically.In response to CBL0137 alone, TIC were more sensitive than non-TIC, in part because CBL0137 increased expression of the tumor suppressor NOTCH1 by abrogating the binding of negative regulator SP3 to the NOTCH1 promoter, and in part because treatment decreased the high expression of stem cell transcription factors. The combination of cisplatin and CBL0137 greatly reduced the growth of a patient-derived xenograft in mice and also the growth of a syngeneic mouse SCLC tumor. Thus, CBL0137 can be a highly effective drug against SCLC, especially in combination with cisplatin. Statement of SignificanceFindings reveal a novel therapeutic regimen for SCLC combining cisplatin with an inhibitor that preferentially targets tumor-initiating cells.

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“…Some researches revealed up-regulation of Bak protein expression, degradation of cyclin D1 and an increase in cyclin-dependent kinases p21 and p27 after sodium valproate treatment. In addition, sodium valproate also increased the levels of full-length Notch-1 and active Notch-1 intracellular domain, which intern inhibit proliferation and induced apoptosis of neoplasm (Greenblatt et al, 2007;Fortunati et al, 2008;Platta et al, 2008). Sami et al in cervical cancer found that sodium valproate can increase the expression of histone H3 acetylation and up-regulate p21 expression (Sami et al, 2008).…”

Section: 6429 Effects Of Sodium Valproate On the Growth Of Human Ovamentioning

confidence: 97%

Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910

Yan

Zhang²

2012

Asian Pacific Journal of Cancer Prevention

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To explore a possible new treatment for human ovarian cancer, we studied the effects of sodium valproate on the growth of the HO8910 human cell line. HO8910 cells were cultured in vitro and treated with different concentrations of sodium valproate. Cell proliferation, cell cycling, and apoptosis were measured by flow cytometry, cell morphology under a microscope, and expression levels of WWOX and P27 by Western blotting and RT-PCR. Tumor xenografts were established to determine in vivo effects of sodium valproate. Our results showed that cell proliferation was decreased with increasing concentration of sodium valproate, with features of cytoplasmic retraction and floating cells. Moreover, cell cycle analysis revealed a higher apoptosis rate and G 0 / G 1 phase in the sodium valproate experimental group than in the control group. In addition, protein expression levels of WWOX and P27 were elevated. Importantly, sodium valproate decreased in vivo xenograft tumor burden and up-regulated WWOX and P27 expression in nude mice. In conclusion, sodium valproate might play a role in inhibition and control of ovarian cancer cell line HO8910 by inhibiting cell proliferation, interfering with the cell cycle and promoting apoptosis, so that it may be effective in the clinical treatment of ovarian cancer. Keywords: Ovarian cancer -apoptosis -WWOX -P27 -sodium valproate RESEARCH ARTICLE Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910Hong-Chao Yan*, Jie Zhang an experimental cell model and the effects of sodium valproate has been investigated on its proliferation, cell cycle, and apoptosis. Materials and Methods Cell CultureHO8910 ovarian cancer cell line, obtained from the Gynecology Department Laboratory of our hospital, Xuzhou, China, were cultured in RPMI 1640 (Hangzhou Sijiqing Biology Engineering Materials Co., Ltd. China) medium supplemented with 10% fetal bovine serum (Hangzhou Sijiqing Biology Engineering Materials Co., Ltd. China), penicillin and streptomycin, in a humidified atmosphere containing 5% CO 2 at 37°C. Experimental groupingThe HO8910 cells were randomly divided into a control group and experiment groups. The experiment groups were cultured in the medium with 1.0, 2.0, 3.0 and 4.0 mmol/L concentrations of sodium valproate (Sigma aldrich, USA), while normal culture medium had been used in the control group. Methylthiazol tetrazolium (MTT) Cell Proliferation AssayMTT cell proliferation assay kit (Beyotime, China) was used for this assay. Briefly, HO8910 cells were trypsinized

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Valproic Acid Induces Notch1 Signaling in Small Cell Lung Cancer Cells

Cited by 59 publications

References 29 publications

Human small cell lung cancer cell line (NCI-H146) tumor behaviour on the chicken embryo chorioallantoic membrane after the sodium valproate treatment

Human small cell lung cancer cell line (NCI-H146) tumor behaviour on the chicken embryo chorioallantoic membrane after the sodium valproate treatment

The FACT inhibitor CBL0137 Synergizes with Cisplatin in Small-Cell Lung Cancer by Increasing NOTCH1 Expression and Targeting Tumor-Initiating Cells

Effects of Sodium Valproate on the Growth of Human Ovarian Cancer Cell Line HO8910

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