scholarly journals Regulation of proliferation of LLC-MK2 cells by nucleosides and nucleotides: the role of ecto-enzymes

1996 ◽  
Vol 316 (2) ◽  
pp. 551-557 ◽  
Author(s):  
Raf LEMMENS ◽  
Luc VANDUFFEL ◽  
Henri TEUCHY ◽  
Ognjen CULIC
Keyword(s):  
Cell Proliferation ◽  
Adenine Nucleotides ◽  
Inhibitory Effect ◽  
Pyrimidine Nucleoside ◽  
Purine Nucleotides ◽  
Pyrimidine Nucleotides ◽  
Nucleotides And Nucleosides ◽  
Nucleoside Uptake ◽  
Stimulate Cell Proliferation

1. Using the incorporation of [methyl-3H]thymidine as a proliferation marker, the effects of various nucleosides and nucleotides on endothelial LLC-MK2 cells were studied. We found that ATP, ADP, AMP and adenosine in concentrations of 10 μM or higher stimulate the proliferation of these cells. 2. Inhibition of ecto-ATPase (EC 3.6.1.15), 5´-nucleotidase (EC 3.1.3.5) or alkaline phosphatase (EC 3.1.3.1) significantly diminished the stimulatory effect of ATP, indicating that the effect is primarily caused by adenosine and not by adenine nucleotides. Also, the effect depends only on extracellular nucleosides, since inhibition of nucleoside uptake by dipyridamole has no influence on proliferation. 3. Other purine nucleotides and nucleosides (ITP, GTP, inosine and guanosine) also stimulate cell proliferation, while pyrimidine nucleotides and nucleosides (CTP, UTP, cytidine and uridine) inhibit proliferation. Furthermore, the simultaneous presence of adenosine and any of the other purine nucleosides is not entirely additive in its effect on cell proliferation. At the same time any pyrimidine nucleoside, when added together with adenosine, has the same inhibitory effect as the pyrimidine nucleoside alone. 4. Apparently these proliferative effects are neither caused by any pharmacologically known P1-purinoceptor, nor are they mediated by cyclic AMP, cyclic GMP, or D-myo-inositol 1,4,5-trisphosphate as second messenger, nor by extracellular Ca2+. 5. Therefore, we conclude that various purine and pyrimidine nucleosides can influence the proliferation of LLC-MK2 cells by acting on putative purinergic and pyrimidinergic receptors not previously described.

LINP1 promotes the progression of cervical cancer by scaffolding EZH2, LSD1, and DNMT1 to inhibit the expression of KLF2 and PRSS8

2020 ◽  
Vol 98 (5) ◽  
pp. 591-599
Author(s):  
Liuli Wu ◽  
Yuan Gong ◽  
Ting Yan ◽  
Huimin Zhang
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Inhibitory Effect ◽  
Loss Of Function ◽  
Healthy Human ◽  
Promising Target ◽  
Epithelial Cell Lines ◽  
Key Factor

There is a growing body of evidence indicating that long non-coding RNAs (lncRNAs) are associated with a variety of cancers. LncRNA LINP1 has been shown to be a key factor in tumor malignancy. However, the role of LINP1 in cervical cancer (CC) it is unclear. In our research, we found that the levels of LINP1 were significantly elevated in CC tissues by comparison with adjacent normal tissue. Further, the expression level of LINP1 was upregulated in CC cells compared with healthy human cervical epithelial cell lines (HUCEC). Surprisingly, we found that downregulation of LINP1 significantly reduced the proliferation of CC cells and promoted apoptosis. Additionally, downregulation of LINP1 significantly decreased CC tumor growth in vivo. Further, we observed that LINP1 recruits EZH2, LSD1, and DNMT1, thereby reducing the expression of KLF2 and PRSS8. The results from our qRT–PCR analyses showed that silencing LINP1 uprgulated the expression of KLF2 and PRSS8 in CC cells. The results from our loss-of-function assays showed that upregulation of KLF2 and PRSS8 inhibits cell proliferation and boosts cell apoptosis in CC. We also found that inhibition of KLF2 and PRSS8 reversed the inhibitory effect on cell proliferation associated with silencing LINP1. In short, LINP1 facilitates the progression of CC by suppressing KLF2 and PRSS8, and thus could provide a promising target for CC therapy.

scholarly journals Biological and physical approaches on the role of piplartine (piperlongumine) in cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiago Henrique ◽  
Caroline de F. Zanon ◽  
Ana P. Girol ◽  
Ana Carolina Buzzo Stefanini ◽  
Nayara S. de A. Contessoto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Physicochemical Analysis ◽  
Biologically Active ◽  
Migration And Invasion ◽  
Annexin A1 ◽  
Anti Inflammatory ◽  
Mimic Peptide

AbstractChronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

TFAP2A-induced SLC2A1-AS1 promotes cancer cell proliferation

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yuanbo Cui ◽  
Chunyan Zhang ◽  
Shanshan Ma ◽  
Fangxia Guan
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Lung Squamous Cell Carcinoma ◽  
Inhibitory Effect ◽  
Cancer Cell Proliferation ◽  
Over Expression ◽  
Enhancer Binding Protein ◽  
Cancer Types

Abstract Long non-coding RNAs (lncRNAs) are involved in the occurrence and development of human cancers including lung adenocarcinoma (LUAD). SLC2A1-AS1 is a novel lncRNA that has been reported to be exceptionally expressed in several cancer types. However, the expression and role of SLC2A1-AS1 in cancer remains largely unclear. In this study, it was revealed that lncRNA SLC2A1-AS1 was notably over-expressed in LUAD and was closely correlated with patients’ overall survival (OS). Knockdown of SLC2A1-AS1 could significantly restrain cell proliferation of LUAD in vitro, while over-expression of SLC2A1-AS1 had the accelerative effect. SLC2A1-AS1 enriched in the cytoplasm of LUAD cells could directly bind to miR-508-5p and negatively regulate its level. The inhibitory effect of miR-508-5p on LUAD cell proliferation was in part abrogated by SLC2A1-AS1 manipulation. Moreover, the transcription factor activating enhancer binding protein 2 α (TFAP2A) was highly expressed in LUAD and predicted worse patients’ OS. TFAP2A could directly bind to the promoter region of SLC2A1-AS1 encoding gene and positively regulate the transcription of SLC2A1-AS1 in LUAD cells. Furthermore, TFAP2A-induced SLC2A1-AS1 promoted cell proliferation of lung squamous cell carcinoma (LUSC) and pancreatic adenocarcinoma (PAAD). Collectively, these findings suggest that TFAP2A-mediated lncRNA SLC2A1-AS1 works as an oncogene to drive cancer cell proliferation.

scholarly journals The Stimulatory Role of CD300a in Diffuse Large B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2975-2975
Author(s):  
Lei Jiang ◽  
Jeff Xiwu Zhou ◽  
Herbert Morse ◽  
Yulian Xu
Keyword(s):  
Cell Proliferation ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Type I ◽  
Expression Levels ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract CD300a is a type I transmembrane receptor protein which has shown inhibitory effect on B-cell receptor mediated signals. In an analysis of publicly available data on diffuse large B-cell lymphoma (DLBCL), however, we found that the expression levels of CD300A mRNA were inversely correlated with the overall survival of DLBCL patients. When analyzing the transcript levels of CD300a in human tissues, we found that CD300a mRNA levels were significantly greater in DLBCL tissues than benign lymphoid tissues (P<0.05). To decipher the role of CD300a in DLBCL, we used shRNA system to knock-down the expression levels of CD300a in DLBCL cell lines, and found that decreased levels of CD300a significantly inhibited cell proliferation of OCI-Ly1 cells, but not of VAL, OCI-Ly10 or SUDHL-8 cells. Mechanistically, reduced expression of CD300a resulted in a marked attenuation of Akt phosphorylation in OCI-Ly1 cells. Pharmacologic inhibition of PI3K by LY294002 displayed a similar inhibitory effect on cell proliferation, indicating the possible involvement of PI3K/Akt signaling pathway in CD300a’s effect. Furthermore, using a xenograft animal model, we found that decreasing expression levels of CD300a in OCI-Ly1 cells significantly inhibited tumor formation of these cells in vivo. Collectively, our results suggested a stimulatory role of CD300a in DLBCL which could serve as a potential biomarker and therapeutic target for this malignance. Disclosures No relevant conflicts of interest to declare.

scholarly journals The long non-coding RNA LINC00473 contributes to cell proliferation via JAK-STAT3 signaling pathway by regulating miR-195-5p/SEPT2 axis in prostate cancer

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Zengshu Xing ◽  
Sailian Li ◽  
Zhenxiang Liu ◽  
Chong Zhang ◽  
Meijiang Meng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Stat3 Signaling Pathway ◽  
High Incidence ◽  
Long Non Coding Rna

Abstract Prostate cancer is a kind of male malignant tumor, which has brought tremendous health threat to men. Prostate cancer is difficult to be cured because of high incidence and metastasis rate. Thereby, it is of great urgency to elucidate the underlying molecular mechanism of prostate cancer for the treatment of this cancer. LINC00473 dysregulation has been observed in many cancers. However, the role of LINC00473 was unknown in prostate cancer. In the present study, we discovered that prostate cancer cells presented high expression of LINC00473, and LINC00473 inhibition limited cell proliferation and the expression of proteins in JAK-STAT3 signaling pathway. Additionally, LINC00473 acted as an up-stream factor for miR-195-5p to negatively modulate miR-195-5p expression. Moreover, SEPT2 interacted with miR-195-5p in prostate cancer and SEPT2 expression was positively modulated by LINC00473 and negatively regulated by miR-195-5p. Last, the inhibitory effect of LINC00473 knockdown on cell proliferation and expression of proteins of JAK-STAT3 signaling pathway was restored by SEPT2 overexpression. All in all, LINC00473 contributed to cell proliferation via JAK-STAT3 signaling pathway by regulating miR-195-5p/SEPT2 axis in prostate cancer, which provided a novel therapeutic tactic for prostate cancer patients.

scholarly journals Prodigiosin inhibits cholangiocarcinoma cell proliferation and induces apoptosis via suppressing SNAREs-dependent autophagy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dijie Zheng ◽  
Shiyu Chen ◽  
Kun Cai ◽  
Linhan Lei ◽  
Chunchen Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Cancer Biology ◽  
Bacterial Species ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Dependent Manner ◽  
Western Blot Assay

Abstract Background Prodigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eye-catching research point in recent years for its anticancer activity. However, the role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague. Methods The proliferation of CCA cells was detected by Cell Counting Kit-8(CCK-8), Colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was evaluated by flow cytometry assay and western blot assay. The effects of PG or SNAREs on cell autophagy were measured by autophagy flux assay and western blot assay. Xenograft mouse models were used to assess the role of PG in CCA cells in vivo. Results PG could inhibit the proliferation and viability of CCA cells in a concentration- and time-dependent manner via suppressing the late stage of autophagy. Mechanistically, PG inhibits the fusion of autophagosomes and lysosomes by blocking STX17 and SNAP29, components of soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs)complex. When STX17 and SNAP29 were overexpressed, the inhibitory effect of PG on CCA cells autophagy was relieved. In addition, PG showed obvious inhibitory effects on cancer cell viability but no toxic effects on organs in xenotransplantation models. Conclusion Taken together, our results demonstrated that PG inhibits CCA cell proliferation via suppressing SNAREs-dependent autophagy, implying that PG could be a potential chemotherapy drug for advanced CCA.

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