scholarly journals Amphipathic Small Molecule AZT Compound Displays Potent Inhibitory Effects in Cancer Cell Proliferation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2071
Author(s):  
Pethaiah Gunasekaran ◽  
Ho Jin Han ◽  
Jung hoon Choi ◽  
Eun Kyoung Ryu ◽  
Nam Yeong Park ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Small Molecule ◽  
Ductal Carcinoma ◽  
Membrane Integrity ◽  
Significant Inhibition ◽  
Cancer Cell Proliferation ◽  
Average Life Expectancy

Cancer has been identified as a leading cause of death worldwide, and the increasing number of cancer cases threatens to shorten the average life expectancy of people. Recently, we reported a 3-azido-3-deoxythymidine (AZT)-based amphipathic small molecule, ADG-2e that revealed a notable potency against tumor metastasis. To evaluate the anticancer potential of ADG-2e, we assessed its anticancer potency in vitro and in vivo. Anticancer screening of ADG-2e against cervical cancer cells, HeLa CCL2, and BT549 mammary gland ductal carcinoma showed significant inhibition of cancer cell proliferation. Furthermore, mechanistic investigations revealed that cancer cell death presumably proceeded through an oncosis mechanistic pathway because ADG-2e treated cells showed severe damage on the plasma membrane, a loss of membrane integrity, and leakage of α-tubulin and β-actin. Finally, evaluation of the antitumorigenic potential of ADG-2e in mouse xenograft models revealed that this compound potentially inhibits cancer cell proliferation. Collectively, these findings suggest that ADG-2e can evolve as an anticancer agent, which may represent a model for nucleoside-based small molecule anticancer drug discovery.

scholarly journals PRMT1-mediated EZH2 methylation promotes breast cancer cell proliferation and tumorigenesis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Zhongwei Li ◽  
Diandian Wang ◽  
Xintian Chen ◽  
Wenwen Wang ◽  
Pengfei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cell Cycle Progression ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Ezh2 Expression

AbstractProtein arginine methyltransferase 1 (PRMT1) is able to promote breast cancer cell proliferation. However, the detailed mechanisms of PRMT1-mediated breast cancer cell proliferation are largely unknown. In this study, we reveal that PRMT1-mediated methylation of EZH2 at the R342 site (meR342-EZH2) has a great effect on PRMT1-induced cell proliferation. We also demonstrate that meR342-EZH2 can accelerate breast cancer cell proliferation in vitro and in vivo. Further, we show that meR342-EZH2 promotes cell cycle progression by repressing P16 and P21 transcription expression. In terms of mechanism, we illustrate that meR342-EZH2 facilitates EZH2 binding with SUZ12 and PRC2 assembly by preventing AMPKα1-mediated phosphorylation of pT311-EZH2, which results in suppression of P16 and P21 transcription by enhancing EZH2 expression and H3K27me3 enrichment at P16 and P21 promoters. Finally, we validate that the expression of PRMT1 and meR342-EZH2 is negatively correlated with pT311-EZH2 expression. Our findings suggest that meR342-EZH2 may become a novel therapeutic target for the treatment of breast cancer.

scholarly journals Exploiting GRK2 Inhibition as a Therapeutic Option in Experimental Cancer Treatment: Role of p53-Induced Mitochondrial Apoptosis

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3530
Author(s):  
Jessica Gambardella ◽  
Antonella Fiordelisi ◽  
Gaetano Santulli ◽  
Michele Ciccarelli ◽  
Federica Andrea Cerasuolo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Nude Mice ◽  
Specific Inhibitor ◽  
Cancer Cell Proliferation ◽  
In Vivo Models ◽  
P53 Expression

The involvement of GRK2 in cancer cell proliferation and its counter-regulation of p53 have been suggested in breast cancer even if the underlying mechanism has not yet been elucidated. Furthermore, the possibility to pharmacologically inhibit GRK2 to delay cancer cell proliferation has never been explored. We investigated this possibility by setting up a study that combined in vitro and in vivo models to underpin the crosstalk between GRK2 and p53. To reach this aim, we took advantage of the different expression of p53 in cell lines of thyroid cancer (BHT 101 expressing p53 and FRO cells, which are p53-null) in which we overexpressed or silenced GRK2. The pharmacological inhibition of GRK2 was achieved using the specific inhibitor KRX-C7. The in vivo study was performed in Balb/c nude mice, where we treated BHT-101 or FRO-derived tumors with KRX-C7. In our in vitro model, FRO cells were unaffected by GRK2 expression levels, whereas BHT-101 cells were sensitive, thus suggesting a role for p53. The regulation of p53 by GRK2 is due to phosphorylative events in Thr-55, which induce the degradation of p53. In BHT-101 cells, the pharmacologic inhibition of GRK2 by KRX-C7 increased p53 levels and activated apoptosis through the mitochondrial release of cytochrome c. These KRX-C7-mediated events were also confirmed in cancer allograft models in nude mice. In conclusion, our data showed that GRK2 counter-regulates p53 expression in cancer cells through a kinase-dependent activity. Our results further corroborate the anti-proliferative role of GRK2 inhibitors in p53-sensitive tumors and propose GRK2 as a therapeutic target in selected cancers.

Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro

2014 ◽  
Vol 134 (2) ◽  
pp. 364-371 ◽  
Author(s):  
Yi Lu ◽  
Lin Zheng ◽  
Wen Zhang ◽  
Tingting Feng ◽  
Juan Liu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Growth Factor ◽  
Cancer Cell ◽  
Cervical Cancer Cell ◽  
Cancer Cell Proliferation

scholarly journals Bauhinia acuminata L. attenuates lung cancer cell proliferation: in vitro, in vivo and in silico approaches

2021 ◽  
pp. 100173
Author(s):  
Divya Sebastian ◽  
K. Gowrishankar ◽  
S. Ignacimuthu ◽  
A.J. Renilda Sophy ◽  
R. Vidhya ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
In Silico ◽  
Cancer Cell Proliferation ◽  
Lung Cancer Cell ◽  
Proliferation In Vitro

Inhibition of Cancer Cell Proliferation in vitro and Tumor Growth in vivo by Hydrophis spiralis Sea Snake Venom

2007 ◽  
Vol 3 (4) ◽  
pp. 186-190
Author(s):  
R. Karthikeya ◽  
S. Karthigaya ◽  
M. Sri Balasubash ◽  
S. Vijayalaks ◽  
S.T. Somasundar ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Snake Venom ◽  
Cancer Cell Proliferation ◽  
Sea Snake ◽  
Proliferation In Vitro

scholarly journals Oncogenic action of the exosome cofactor RBM7 by stabilization of CDK1 mRNA in breast cancer

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Pei-Wen Xi ◽  
Xu Zhang ◽  
Lei Zhu ◽  
Xin-Yuan Dai ◽  
Lin Cheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Rna Binding ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Rna Exosome

Abstract RNA exosome can target the specific RNAs for their processing/degradation by distinct exosome cofactors. As a key component in exosome cofactors, RNA binding motif protein 7 (RBM7) shows the binding specificity for uridine-rich sequences in mRNAs via its RNA recognition motifs. However, the specific function of RBM7 in human breast cancer remains unclear. In vitro, experiments revealed that knockdown of RBM7 dramatically inhibited breast cancer cell proliferation, while inducing G1 cell cycle arrest; the opposite was true when RBM7 was overexpressed. Meanwhile, experiments in vivo confirmed the oncogenic function of RBM7 in breast cancer. RNA sequencing and the following pathway analysis found that cyclin-dependent kinase1 (CDK1) was one of the main gene regulated by RBM7. Overexpression of RBM7 increased CDK1 expression, while RBM7 knockdown decreased it. RIP assays additionally found that RBM7 bound directly to CDK1 mRNA. It was also showed that RBM7 could directly bind to the AU-rich elements (AREs) in 3′-UTR of CDK1 mRNA, which contributed to the stability of CDK1 mRNA by lengthening its half-life. More importantly, the oncogenic activity reduced by knockdown of RBM7 could be rescued by overexpression of CDK1 both in vitro and in vivo, but mutant CDK1 failed. All the evidences implied RBM7 promoted breast cancer cell proliferation by stabilizing CDK1 mRNA via binding to AREs in its 3′-UTR. As we knew, it was the first attempt to connect the RNA exosome to the tumor development, providing new insights into the mechanisms of RNA exosome-linked diseases.

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