scholarly journals Inhibition of tumor cell growth by adenine is mediated by apoptosis induction and cell cycle S phase arrest

Oncotarget ◽  
2017 ◽  
Vol 8 (55) ◽  
pp. 94286-94296 ◽  
Author(s):  
Ming Han ◽  
Xin Cheng ◽  
Zhiqin Gao ◽  
Rongrong Zhao ◽  
Shizhuang Zhang
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
S Phase ◽  
Tumor Cell Growth ◽  
Apoptosis Induction ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals Naringenin Enhances the Anti-Tumor Effect of Doxorubicin on HeLa Cervical Cancer Cells Through Cytotoxic Activity and Apoptosis Induction

2011 ◽  
Vol 2 (3) ◽  
pp. 325 ◽  
Author(s):  
Larasati Larasati ◽  
Indri Kusharyanti ◽  
Adam Hermawan ◽  
Ratna Asmah Susidarti ◽  
Edy Meiyanto
Keyword(s):  
Cell Cycle ◽  
Cervical Cancer ◽  
Hela Cells ◽  
Cytotoxic Effect ◽  
S Phase ◽  
Apoptosis Induction ◽  
Double Staining ◽  
Single Treatment ◽  
Phase Arrest ◽  
S Phase Arrest

Naringenin, an abundant flavanon in the peel of citrus fruits is reported to possess anti-proliferative effect in many cancer cells. Herein, we investigated the cytotoxic effect and apoptosis induction of naringenin in combination with doxorubicin on HeLa cells. The cytotoxicity assay of naringenin, doxorubicin, and their combination were carried out by using MTT assay. Cell viability was used as the parameters to evaluate combination effectiveness. Cell cycle distribution was determined by flow cytometry and analyzed using ModFit LT 3.0 program. Apoptosic assay was done by double staining method using Ethidium Bromide-Acridine Orange. Investigation on the expression of Bax and Bcl-2 were determined by immunocytochemistry method. Naringenin and doxorubicin showed cytotoxic effect on HeLa cells with their IC50 values of 195 µM and 1 µM, respectively. Whereas combination of naringenin - doxorubicin showed greater cytotoxicity compared the single treatment of doxorubicin. The strongest cytotoxic activity was observed at a combination of 100 µM naringenin and 0,5 µM doxorubicin. Single treatment of 0,5 µM doxorubicin for 24 hours on HeLa cells induced S-phase arrest while 100 µM naringenin did not affect on HeLa cell cycle. The combination induced S-phase arrest with the increased of sub-G1 phase percentage. In accordance with the flow cytometry results, the double staining apoptosis assay results showed the increase of apoptotic cells. Naringenin, doxorubicin, and their combination also increased the expression of Bax and decreased the expression of Bcl-2. These results concluded that naringenin was a potential co-chemotherapy agent for cervical cancer due to its synergism with doxorubicin.Keywords: co-chemotherapy, naringenin, doxorubicin, HeLa cells, cytotoxicity, cell cycle, apoptosis

Thrombin Enhances Spontaneous Tumor Growth and Cell Cycle Activation by Downregulation of p27Kip1 and Upregulation of Skp2 and MiR-222

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 396-396
Author(s):  
Liang Hu ◽  
Sherif Ibrahim ◽  
Cynthia Liu ◽  
Jeffrey Skaar ◽  
Michelle Pagano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factors ◽  
Cell Growth ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Tumor Volume ◽  
S Phase ◽  
Down Regulation

Abstract Although it has been generally accepted that hypercoagulability contributes to enhancing tumor growth via generation of thrombin (Cancer Cell10:355, 2006), it has not been rigorously proven, nor has the mechanism been established at the cell cycle level. Previous studies have employed thrombin-treated tumor cell lines in vitro and in vivo. In vitro studies were performed in the presence of serum which contains a panoply of growth factors. In vivo studies have used huge non-pathologic concentrations of tumor cells injected into the flank, organ or blood of a mouse. In these situations, tumor growth could be a result of thrombin-induced angiogenesis. We therefore employed a transgenic mouse prostate cancer model (TRAMP) programmed to develop prostate CA over a period of 140–175 days. We treated these animals with thrombin to induce hypercoagulability or hirudin to inhibit endogenous thrombin production, to determine whether thrombin regulates this process independent of angiogenesis. Repetitive thrombin injection enhanced prostate tumor volume 6–8 fold (p<0.04). Repetitive hirudin decreased tumor volume 13–24 fold (p<0.04) via its effect on generated endogenous thrombin, n=6. Thrombin enhanced the production of several vascular growth factors and receptors 2.5 – 3 fold in the liver (VEGF, KDR, ANG-2, Tie2, GRO-1, CD31) and enhanced angiogenesis in the liver, n=3–4. Thrombin had no effect on tumor angiogenesis. Thus, the thrombin-induced spontaneous tumor growth was independent of angiogenesis. We next turned our attention to cell cycle regulators in serum-starved (72 hr) Go-synchronized LNcap prostate CA cells, employing Brdu and Propidium iodide staining. Addition of thrombin (0.5 u/ml) or its PAR-1 receptor agonist, TFLLRN (100 uM) had the same effect as androgen containing serum, inducing cells to leave Go, enter G1 and progress to S-phase. At 8 hrs the number of S-phase cells increased dramatically for both the serum (29 fold) as well as thrombin-treated cells (48 fold), n=3. Similar observations were noted in a Glioblastoma cell line, T98G. We further analyzed the effect of thrombin by performing immunoblots on cell cycle components mediated during cell growth and proliferation. In synchronized Go cells, levels of p27Kip1, a cyclin-dependent kinase inhibitor are high, while levels of cyclins D1 and A, the activation subunits for cyclin-dependent kinases are low. Both thrombin or serum addition led to down-regulation of p27Kip1 with concomitant induction of Skp2, the E3 ubiquitin ligase for p27Kip1. Cyclins D1 and A are induced by similar kinetics, indicating entry into S-phase by 8 hrs. Since p27Kip1 appears to be a rate-limiting down-regulator of the cell cycle (absent with high tumor grade and predicts poor prognosis), we confirmed its role by testing the effect of thrombin or TFLLRN by transfecting p27Kip1 in LNcap cells. This transfection completely prevented the cell cycle stimulation induced by these agonists. A similar approach was used with Skp2 knock down (KD), a negative down-regulator of p27Kip1. KD of Skp2 (over expressed in numerous cancers) completely prevented cell cycle progression induced by thrombin/TFLLRN. MiRNA 222 (upregulated in many cancers) is another down-regulator of p27Kip1. Further analysis following thrombin treatment revealed a robust upregulation at 4 and 8 hrs, providing further proof for the role of thrombin in down-regulating p27Kip1 and stimulating tumor cell entrance into S-phase. Thus, 1) Thrombin enhances spontaneous prostate cell growth in vivo in the absence of enhanced angiogenesis; 2) Thrombin activates the tumor cell cycle by stimulating the down-regulation of p27Kip1 through the upregulation of Skp2 and MiRNA 222.

Antimycin A as a mitochondria damage agent induces an S phase arrest of the cell cycle in HeLa cells

Life Sciences ◽  
2008 ◽  
Vol 83 (9-10) ◽  
pp. 346-355 ◽  
Author(s):  
Yong Hwan Han ◽  
Suhn Hee Kim ◽  
Sung Zoo Kim ◽  
Woo Hyun Park
Keyword(s):  
Cell Cycle ◽  
Hela Cells ◽  
S Phase ◽  
Antimycin A ◽  
Phase Arrest ◽  
S Phase Arrest

Synthesis of a Natural Chalcone and Its Prenyl Analogs - Evaluation of Tumor Cell Growth-Inhibitory Activities, and Effects on Cell Cycle and Apoptosis

2012 ◽  
Vol 9 (6) ◽  
pp. 1133-1143 ◽  
Author(s):  
Marta P. Neves ◽  
Raquel T. Lima ◽  
Kanthima Choosang ◽  
Panee Pakkong ◽  
Maria de São José Nascimento ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Growth Inhibitory ◽  
Inhibitory Activities

Inhibition of tumor cell growth by triton X-100 through specific effects on cell-cycle-regulatory components

2004 ◽  
Vol 11 (1) ◽  
pp. 95-103 ◽  
Author(s):  
Esther R. Picache ◽  
Loubna Hassanieh ◽  
Daniel Broek ◽  
Axel H. Schönthal
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Tumor Cell ◽  
Tumor Cell Growth ◽  
Specific Effects ◽  
Triton X

scholarly journals p21Cip1 and p27Kip1Regulate Cell Cycle Reentry after Hypoxic Stress but Are Not Necessary for Hypoxia-Induced Arrest

2001 ◽  
Vol 21 (4) ◽  
pp. 1196-1206 ◽  
Author(s):  
Susannah L. Green ◽  
Rachel A. Freiberg ◽  
Amato J. Giaccia
Keyword(s):  
Cell Cycle ◽  
Dna Synthesis ◽  
Kinase Inhibitors ◽  
S Phase ◽  
Hypoxic Stress ◽  
Cyclin Dependent Kinase ◽  
Low Oxygen ◽  
Double Knockout ◽  
Phase Arrest ◽  
S Phase Arrest

ABSTRACT We investigated the role of the cyclin-dependent kinase inhibitors p21Cip1 and p27Kip1 in cell cycle regulation during hypoxia and reoxygenation. While moderate hypoxia (1 or 0.1% oxygen) does not significantly impair bromodeoxyuridine incorporation, at very low oxygen tensions (0.01% oxygen) DNA replication is rapidly shut down in immortalized mouse embryo fibroblasts. This S-phase arrest is intact in fibroblasts lacking the cyclin kinase inhibitors p21Cip1 and p27Kip1, indicating that these molecules are not essential elements of the arrest pathway. Hypoxia-induced arrest is accompanied by dephosphorylation of pRb and inhibition of cyclin-dependent kinase 2, which results in part from inhibitory phosphorylation. Interestingly, cells lacking the retinoblastoma tumor suppressor protein also display arrest under hypoxia, suggesting that pRb is not an essential mediator of this response. Upon reoxygenation, DNA synthesis resumes by 3.5 h and reaches aerobic levels by 6 h. Cells lacking p21, however, resume DNA synthesis more rapidly upon reoxygenation than wild-type cells, suggesting that this inhibitor may play a role in preventing premature reentry into the cell cycle upon cessation of the hypoxic stress. While p27 null cells did not exhibit rapid reentry into the cell cycle, cells lacking both p21 and p27 entered S phase even more aggressively than those lacking p21 alone, revealing a possible secondary role for p27 in this response. Cdk2 activity is also restored more rapidly in the double-knockout cells when returned to normoxia. These studies reveal that restoration of DNA synthesis after hypoxic stress, but not the S phase arrest itself, is regulated by p21 and p27.

Methimazole inhibits FRTL5 thyroid cell proliferation by inducing S-phase arrest of the cell cycle.

Endocrinology ◽  
1993 ◽  
Vol 133 (5) ◽  
pp. 2403-2406 ◽  
Author(s):  
P Smerdely ◽  
V Pitsiavas ◽  
S C Boyages
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
S Phase ◽  
Thyroid Cell ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals Cell Cycle Modulation by Marek’s Disease Virus: The Tegument Protein VP22 Triggers S-Phase Arrest and DNA Damage in Proliferating Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e100004 ◽  
Author(s):  
Laëtitia Trapp-Fragnet ◽  
Djihad Bencherit ◽  
Danièle Chabanne-Vautherot ◽  
Yves Le Vern ◽  
Sylvie Remy ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Disease Virus ◽  
S Phase ◽  
Tegument Protein ◽  
Proliferating Cells ◽  
Phase Arrest ◽  
Cell Cycle Modulation ◽  
S Phase Arrest ◽  
Protein Vp22
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