scholarly journals Copper complexes as prospective anticancer agents: in vitro and in vivo evaluation, selective targeting of cancer cells by DNA damage and S phase arrest

RSC Advances ◽  
2018 ◽  
Vol 8 (30) ◽  
pp. 16973-16990 ◽  
Author(s):  
Dharmasivam Mahendiran ◽  
Sethu Amuthakala ◽  
Nattamai S. P. Bhuvanesh ◽  
Raju Senthil Kumar ◽  
Aziz Kalilur Rahiman
Keyword(s):  
Dna Damage ◽  
Anticancer Agents ◽  
Copper Complexes ◽  
S Phase ◽  
In Vivo Evaluation ◽  
Phase Arrest ◽  
Selective Targeting ◽  
S Phase Arrest

The thiosemicarbazone-based copper(i) complexes causing S phase arrest and apoptosis involving the mitochondrial controlled pathway has been investigated.

Water-soluble oxoglaucine-Y(iii), Dy(iii) complexes: in vitro and in vivo anticancer activities by triggering DNA damage, leading to S phase arrest and apoptosis

2015 ◽  
Vol 44 (25) ◽  
pp. 11408-11419 ◽  
Author(s):  
Jian-Hua Wei ◽  
Zhen-Feng Chen ◽  
Jiao-Lan Qin ◽  
Yan-Cheng Liu ◽  
Zhu-Quan Li ◽  
...  
Keyword(s):  
Dna Damage ◽  
Anticancer Activity ◽  
S Phase ◽  
Water Soluble ◽  
Anticancer Activities ◽  
Phase Arrest ◽  
S Phase Arrest

The complexes exhibited considerable in vitro and in vivo anticancer activity, and higher safety than ciplatin.

scholarly journals Phytoestrogen Bakuchiol Exhibits In Vitro and In Vivo Anti-breast Cancer Effects by Inducing S Phase Arrest and Apoptosis

2016 ◽  
Vol 7 ◽  
Author(s):  
Li Li ◽  
Xueping Chen ◽  
Chi C. Liu ◽  
Lai S. Lee ◽  
Cornelia Man ◽  
...  
Keyword(s):  
Breast Cancer ◽  
S Phase ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals Ganoderma tsugaeInduces S Phase Arrest and Apoptosis in Doxorubicin-Resistant Lung Adenocarcinoma H23/0.3 Cells via Modulation of the PI3K/Akt Signaling Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Yang-Hao Yu ◽  
Han-Peng Kuo ◽  
Hui-Hsia Hsieh ◽  
Jhy-Wei Li ◽  
Wu-Huei Hsu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
S Phase ◽  
Akt Signaling Pathway ◽  
Suppression Effect ◽  
Phase Arrest ◽  
S Phase Arrest

Ganoderma tsugae(GT) is a traditional Chinese medicine that exhibits significant antitumor activities against many types of cancer. This study investigated the molecular mechanism by which GT suppresses the growth of doxorubicin-resistant lung adenocarcinoma H23/0.3 cells. Our results reveal that GT inhibits the viability of H23/0.3 cellsin vitroandin vivoand sensitizes the growth suppression effect of doxorubicin on H23/0.3 cells. The data also show that GT induces S phase arrest by interfering with the protein expression of cyclin A, cyclin E, CDK2, and CDC25A. Furthermore, GT induces cellular apoptosis via induction of a mitochondria/caspase pathway. In addition, we also demonstrate that the suppression of cell proliferation by GT is through down-regulation of the PI3K/Akt signaling pathway. In conclusion, this study suggests that GT may be a useful adjuvant therapeutic agent in the treatment of lung cancer.

scholarly journals Selenocystine inhibits JEG-3 cell growth in vitro and in vivo by triggering oxidative damage-mediated S-phase arrest and apoptosis

2018 ◽  
Vol 14 (7) ◽  
pp. 1540 ◽  
Author(s):  
Zhigang Wei ◽  
Ming Zhao ◽  
Yajun Hou ◽  
Xiaoting Fu ◽  
Dawei Li ◽  
...  
Keyword(s):  
Cell Growth ◽  
Oxidative Damage ◽  
S Phase ◽  
Phase Arrest ◽  
S Phase Arrest

scholarly journals RSK Inhibition Suppresses AML Proliferation through Activation of DNA Damage Pathways and S Phase Arrest

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2894-2894 ◽  
Author(s):  
Ritika Dutta ◽  
Maria Castellanos ◽  
Bruce Tiu ◽  
Hee-Don Chae ◽  
Kara L. Davis ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Cell Growth ◽  
Cell Lines ◽  
Conflicts Of Interest ◽  
S Phase ◽  
Hematopoietic Stem ◽  
Phase Arrest ◽  
S Phase Arrest

Abstract The 90 kDa Ribosomal S6 Kinase (RSK), downstream of the ERK signaling pathway, has recently been implicated in a wide variety of cancers, ranging from lung cancer to medulloblastoma, as a driver of cancer cell proliferation and survival. However, its role in Acute Myeloid Leukemia (AML) remains unknown. Thus, the goal of this study was to characterize RSK-dependent signaling pathways in AML, with the overall hypothesis that disruption of this pathway represents a potential strategy for the treatment of AML. The RSK family consists of four gene isoforms, RSK1-4 (RPS6KA1 (RSK1), RPS6KA2 (RSK3), RPS6KA3 (RSK2), RPS6KA4 (RSK4). Knockdown (KD) of RSK1 by shRNA in HL-60 and KG-1 cell lines resulted in reduced AML cell growth in vitro. NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were injected with 2x106 HL-60 or KG-1 RSK1KD cells and vector control transduced cells in order to investigate the effects of RSK1 KD on AML cell growth and survival in vivo. Mice injected with RSK1 KD cells exhibited prolonged survival by 17 and 21 days respectively for HL-60 and KG-1 cell induced disease (p=0.0023 and 0.0018 respectively). These data indicate that RSK1 knockdown inhibits leukemia progression, and RSK1 is required for maximal proliferation of AML cells in vivo. Pharmacological inhibition of total RSK (RSK1-4) by the small molecule inhibitor BI-D1870 reduced AML cell growth and induced cell death in both AML cell lines and patient samples after treatment for 48 hours. The IC50 for growth inhibition was 1.8 uM for MOLM-13, 1.6 uM for MV-4-11, and 1.9 uM for HL-60 cells. In methylcellulose colony assays, normal hematopoietic stem and progenitor cell proliferation was not affected by RSK inhibition up to a concentration of 15 uM, establishing an approximately 10-fold therapeutic index. To elucidate the mechanism by which RSK inhibition suppresses AML proliferation, we performed cell cycle analysis with HL-60 cells. RSK inhibition by BI-D1870 resulted in delayed S-phase progression and accumulation of cells in late S-phase with increased pH2AX, cPARP, and CDK2/Cyclin A expression, as measured by flow cytometry. These data indicate that inhibition of RSK leads to activation of DNA damage pathways and arrest in S-phase, resulting in apoptosis. Inhibition of CDK activity rescued S-phase arrest, demonstrating that activation and dysregulation of CDK are crucial mediators of RSK inhibitor-induced S-phase arrest. In summary, this is the first study to demonstrate that RSK plays an important role in maintaining AML cell survival and proliferation and to position RSK as a promising target for treatment of AML. Disclosures No relevant conflicts of interest to declare.

scholarly journals Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo

2019 ◽  
Vol 20 (13) ◽  
pp. 3197 ◽  
Author(s):  
Takanori Matsui ◽  
Taiga Chiyo ◽  
Hideki Kobara ◽  
Shintaro Fujihara ◽  
Koji Fujita ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
S Phase ◽  
Phase Arrest ◽  
S Phase Arrest

Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.

scholarly journals Betulinic Acid Induces ROS-Dependent Apoptosis and S-Phase Arrest by Inhibiting the NF-κB Pathway in Human Multiple Myeloma

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Min Shen ◽  
Yiqiang Hu ◽  
Yan Yang ◽  
Lanlan Wang ◽  
Xin Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Betulinic Acid ◽  
Redox Homeostasis ◽  
Xenograft Model ◽  
S Phase ◽  
Phase Arrest ◽  
S Phase Arrest ◽  
Human Multiple Myeloma

Betulinic acid (BA), as a prospective natural compound, shows outstanding antitumor bioactivities against many solid malignancies. However, its mechanism against multiple myeloma (MM) remains elusive. Herein, for the first time, we studied the antitumor activity of BA against MM both in vivo and in vitro. We showed that BA mediated cytotoxicity in MM cells through apoptosis, S-phase arrest, mitochondrial membrane potential (MMP) collapse, and overwhelming reactive oxygen species (ROS) accumulation. Moreover, when the ROS scavenger N-acetyl cysteine (NAC) effectively abated elevated ROS, the BA-induced apoptosis was partially reversed. Our results revealed that BA-mediated ROS overproduction played a pivotal role in anticancer activity. Molecularly, we found that BA resulted in marked inhibition of the aberrantly activated NF-κB pathway in MM. As demonstrated by using the NF-κB pathway-specific activator TNF-α and the inhibitor BAY 11-7082, BA-mediated inhibition of the NF-κB pathway directly promoted the overproduction of ROS and, ultimately, cell death. Furthermore, BA also exerted enormous tumor-inhibitory effects via repressing proliferation and inhibiting the NF-κB pathway in our xenograft model. Overall, by blocking the NF-κB pathway that breaks redox homeostasis, BA, as a potent NF-κB inhibitor, is a promising therapeutic alternative for MM.

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