Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells

2019 ◽  
Vol 10 (11) ◽  
pp. 7253-7261
Author(s):  
Jiangxia Zheng ◽  
Xian Cheng ◽  
Shichen Xu ◽  
Li Zhang ◽  
Jie Pan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Anaplastic Thyroid Carcinoma ◽  
Diallyl Trisulfide ◽  
M Cell ◽  
Cycle Arrest

DATS induces G2/M cell-cycle arrest and apoptosis through ATM-Chk1-Cdc25C signaling pathway in ATC 8505C cells.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

The intracellular genistein metabolite 5,7,3′,4′-tetrahydroxyisoflavone mediates G2-M cell cycle arrest in cancer cells via modulation of the p38 signaling pathway

2006 ◽  
Vol 41 (8) ◽  
pp. 1225-1239 ◽  
Author(s):  
Dominique T. Nguyen ◽  
Eva Hernandez-Montes ◽  
David Vauzour ◽  
Axel H. Schönthal ◽  
Catherine Rice-Evans ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
M Cell ◽  
Cycle Arrest

scholarly journals HRT, Herbal Formula, Induces G2/M Cell Cycle Arrest and Apoptosis via Suppressing Akt Signaling Pathway in Human Colon Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Nam-Hui Yim ◽  
Won-Kyung Cho ◽  
Ju Hye Lee ◽  
Young Pil Jung ◽  
Hye Jin Yang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
M Cell ◽  
Human Colon Cancer ◽  
Cycle Arrest

We have demonstrated the anticancer effect of HRT in HCT116, human colon carcinoma cells. HRT inhibited cancer cell growth by causing cell cycle arrest at G2/M and inducing apoptosis as evidenced by DNA fragmentation assay. We found that HRT induces the activation of caspase-3, -8, and -9, whereas it reduces the level of Bcl-2 protein and results in the cleavage of PARP. Further, HRT decreased the level of phosphorylation of Akt and its downstream signals such as mTOR and GSK-3β. These results indicate that HRT stimulates the apoptotic signaling pathway and represses the survival and proliferation of colon cancer cells via inhibiting Akt activity. Hence, our results suggest that HRT has a potential to be developed as a therapeutic agent against colon cancer cells.

The HGF/c-Met Signaling Pathway in Hodgkin Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1551-1551
Author(s):  
Chuanhui Xu ◽  
Anke Van Den Berg ◽  
Arjan Diepstra ◽  
Miao Wang ◽  
Debora Jong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cell Cycle Arrest ◽  
Hodgkin Lymphoma ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cell Cycle Progression ◽  
M Cell ◽  
Cycle Progression ◽  
Cycle Arrest

Abstract Abstract 1551 Poster Board I-574 Introduction Hodgkin lymphoma (HL) is a B-cell neoplasm characterized by a minority of neoplastic cells, the so-called Hodgkin and Reed-Sternberg (HRS) cells, which are located within an extensive infiltrate of reactive cells. Aberrant signaling of various receptor tyrosine kinases (RTKs) via autocrine or paracrine mechanisms contributes to the survival and proliferation of HRS cells. Activation of the hepatocyte growth factor (HGF)/c-Met signaling pathway has been implicated in the pathophysiology of many cancers, but its role in HL is poorly investigated. In this study, we investigated the expression of c-Met and HGF in HL patient tissues and studied the cell physiological effects of the HGF/c-Met signaling pathway using a c-Met tyrosine kinase inhibitor SU11274 in HL cell lines. Methods The expression of c-Met and HGF in HL patient tissues was studied by immunohistochemistry on a HL tissue microarray. The c-Met expression level was determined by Western blotting, while HGF mRNA and protein levels were measured by quantitative (q)RT-PCR and ELISA in four HL cell lines, i.e. L428, KMH2, L1236 and U-HO1. The effects of SU11274 treatment on the activity of the HGF/c-Met signaling pathway was determined by detection of phosphorylated downstream targets by Western blotting. Effects on cell growth and cell cycle were determined by 3-(4,5- Dimethylthiazol -2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and by flow cytometry with Propidium iodide (PI), respectively. Results C-Met was detected in HRS cells in 55% (26/47) of HL patient tissues. Expression of HGF was detected in HRS cells in 5 c-Met positive and 2 c-Met negative HL patient tissues. C-Met was highly expressed in L428 compared to three other HL cell lines, whereas HGF was highly expressed in KMH2 and not or only weakly in the other three HL cell lines. Detectable levels of phosphorylated c-Met (p-Met) were observed only in L428 consistent with the high basal expression level of c-Met. Phosphorylation of c-Met, Akt and Erk1/2 were upregulated upon HGF stimulation of L428 cells. This activation could be blocked by inhibiting c-Met activation with SU11274. In functional studies, SU11274 suppressed cell growth in L428, promoted G2/M cell cycle arrest after 24h incubation, and induced tetraploidy after 48h. Washing of the cells after induction of G2/M arrest resulted in normal cell cycle progression indicating that the G2/M cell cycle arrest was reversible. Inhibition of PI3K, MEK1/2 and Erk1/2, three downstream targets of the HGF/c-Met signaling pathway, also induced G2/M cell cycle arrest in L428, indicating that these factors are involved in the G2/M cell cycle arrest induced by SU11274. Conclusion Co-expression of c-Met and HGF in HRS cells was observed in 11% of the HL patient tissues and HGF/c-Met signaling pathway regulates cell growth and cell cycle progression in L428 cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals HDAC1 and HDAC2 Double Knockout Triggers Cell Apoptosis in Advanced Thyroid Cancer

2019 ◽  
Vol 20 (2) ◽  
pp. 454 ◽  
Author(s):  
Ching-Ling Lin ◽  
Ming-Lin Tsai ◽  
Chun-Yu Lin ◽  
Kai-Wen Hsu ◽  
Wen-Shyang Hsieh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Histone Acetylation ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Anaplastic Thyroid Carcinoma ◽  
Double Knockout ◽  
Cycle Arrest ◽  
Advanced Thyroid Cancer

Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.

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