The tumor-promoting activity of 2-acetylaminofluorene is associated with disruption of the p53 signaling pathway and the balance between apoptosis and cell proliferation☆

2009 ◽  
Vol 235 (3) ◽  
pp. 305-311 ◽  
Author(s):  
Igor P. Pogribny ◽  
Levan Muskhelishvili ◽  
Volodymyr P. Tryndyak ◽  
Frederick A. Beland
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
P53 Signaling ◽  
P53 Signaling Pathway

scholarly journals PPM1D Knockdown Suppresses Cell Proliferation, Promotes Cell Apoptosis, and Activates p38 MAPK/p53 Signaling Pathway in Acute Myeloid Leukemia

2020 ◽  
Vol 19 ◽  
pp. 153303382094231
Author(s):  
Bin Li ◽  
Jie Hu ◽  
Di He ◽  
Qi Chen ◽  
Suna Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Protein Phosphatase ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
P53 Signaling ◽  
P53 Signaling Pathway ◽  
Acute Myeloid

Objectives: This study was to explore the effect of protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown on proliferation and apoptosis as well as p38 MAPK/p53 signaling pathway in acute myeloid leukemia. Methods: The expression of protein phosphatase, Mg2+/Mn2+ dependent 1D was detected in acute myeloid leukemia cell lines including SKM-1, KG-1, AML-193, and THP-1 cells, and normal bone marrow mononuclear cells isolated from healthy donors. The knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D was conducted by transfecting small interfering RNA into AML-193 cells and KG-1 cells. Results: The relative messenger RNA/protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were higher in SKM-1, KG-1, AML-193, and THP-1 cells compared with control cells (normal bone marrow mononuclear cells). After transfecting protein phosphatase, Mg2+/Mn2+ dependent 1D small interfering RNA into AML-193 cells and KG-1 cells, both messenger RNA and protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were significantly reduced, indicating the successful transfection. Most importantly, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D suppressed cell proliferation and promoted cell apoptosis in AML-193 cells and KG-1 cells. In addition, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D enhanced the expressions of p-p38 and p53 in AML-193 cells and KG-1 cells. The above observation suggested that protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown suppressed cell proliferation, promoted cell apoptosis, and activated p38 MAPK/p53 signaling pathway in acute myeloid leukemia cells. Conclusion: Protein phosphatase, Mg2+/Mn2+ dependent 1D is implicated in acute myeloid leukemia carcinogenesis, which illuminates its potential role as a treatment target for acute myeloid leukemia.

scholarly journals Effects of microRNA-374 on proliferation, migration, invasion, and apoptosis of human SCC cells by targeting Gadd45a through P53 signaling pathway

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Xiao-Jing Li ◽  
Zhi-Feng Li ◽  
Jiu-Jiang Wang ◽  
Zhao Han ◽  
Zhao Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Normal Skin ◽  
Negative Control ◽  
Migration And Invasion ◽  
Caspase 9 ◽  
P53 Signaling ◽  
P53 Signaling Pathway ◽  
Skin Samples

The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 α (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA–Gadd45a, and miR-374 inhibitors + siRNA–Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA–Gadd45a group showed decreased miR-374 level; the siRNA–Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a.

scholarly journals LncRNA GClnc1 may contribute to the progression of ovarian cancer by regulating p53 signaling pathway

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Hu Li ◽  
Zheng Zeng ◽  
Xiang Yang ◽  
Ye Chen ◽  
Lei He ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Gynecological Malignancy ◽  
P53 Signaling ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
P53 Signaling Pathway ◽  
Proliferation And Migration

Ovarian cancer (OC) is one of the most prevalent and deadly types of gynecological malignancy. Since current treatments are not effective against OC, it is imperative to develop novel potential therapeutic targets for managing OC. In this study, we aimed to uncover the underlying molecular mechanism of long non-coding RNA (lncRNA) GClnc1 related to p53 signaling pathway in OC. The expression of lncRNA H19 GClnc1 was markedly higher in OC samples than the related normal tissues. Next, we found that lncRNA GClnc1 inhibited p53. In addition, the lncRNA GClnc1 overexpression promoted the cell proliferation and migration in vitro. Subsequently, p53 silencing obligated the effect of lncRNA GCln1 knock down on cell proliferation and migration. To sum up, LncRNA GClnc1 contributes to the progression of OC by regulating p53 signaling pathway. Meanwhile, our findings also suggested that lncRNA GClnc1 may serve as a novel therapeutic target for OC patients.

Chiaurinib Selectively Inhibits Colorectal Cancer with KRAS Wild-Type by Modulation of ROS through Activating the p53 Signaling Pathway

2020 ◽  
Author(s):  
Haofan Yin ◽  
Jineye Xie ◽  
Ping Jiang ◽  
Xi Jiang ◽  
Deyu Duan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Ros Production ◽  
Wild Type ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract Background: Colorectal cancer (CRC) is one of the top three most deadly cancers despite using chemotherapy based on oxaliplatin or irinotecan combined with targeted therapy. Chiaurinib has recently been identified to be a promising anticancer candidate with impressive efficacy and safety. However, the role and molecular mechanisms of Chiaurinib in the treatment of CRC remain to be elucidated.Methods: Cell proliferation and apoptosis were detected by CCK-8, EDU staining, Colony formation assay, TUNEL staining and flow cytometric analysis. ROS production was confirmed by Mito-SOX and DCF-DA fluorescence. RNA-Seq and GSEA analysis were used to explore the mechanisms of the effect of Chiaurinib in KRAS wild-type CRC cells.Results: Our study shows that Chiaurinib inhibits cell proliferation and induces apoptosis in KRAS wild-type CRC cells in a dose- and time-dependent manner, but not mutation ones. Meanwhile, Chiaurinib increases ROS production in KRAS wild-type CRC cells. Moreover, Chiaurinib selectively suppresses KRAS wild-type CRC cells growth in vivo. Mechanistically, Chiaurinib inhibits KRAS wild-type CRC cells by triggering ROS production via activating the p53 signaling pathway. Further, KRAS mutation CRC cells are resistant to Chiaurinib by increasing Nrf2 to stably elevate the basal antioxidant program and thereby lower intracellular ROS induced by Chiaurinib.Conclusions: Taken together, we reveal that Chiauranib induces p53 upregulation, resulting in ROS accumulation, thus inhibiting cell proliferation and inducing apoptosis in KRAS wild-type CRC cells. Our findings provide the rationale for further clinical evaluation of Chiaurinib as a therapeutic agent in treating KRAS wild-type CRC.

Bursal Hexapeptide, A Potential Immunomodulator, Inhibits Tumor Cells Proliferation via p53 Signaling Pathway

2019 ◽  
Vol 18 (11) ◽  
pp. 1582-1588
Author(s):  
Cong Zhang ◽  
Jiangfei Zhou ◽  
Shengnan Li ◽  
Kairui Cai ◽  
Xiangling Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Bursa Of Fabricius ◽  
Dependent Manner ◽  
Humoral Immune ◽  
P53 Signaling ◽  
Regulated Expression ◽  
Microarray Analyses ◽  
P53 Signaling Pathway

Background: The Bursa of Fabricius (BF) is acknowledged as the central humoral immune organ unique to birds. Bursal Hexapeptide (BHP, AGCCNG) is a recently reported bursal-derived bioactive peptide. However, there are few reports of the molecular basis of the mechanism on immune induction and potential antitumor activity of BHP. Method: In this paper, Gene microarray analyses demonstrated that BHP regulated expression of 1347 genes, of which 832 were up-regulated and 515 were down-regulated. Differentially expressed genes involved in various pathways were identified, of which 16 pathways were associated with immune responses and tumorigenic processes. Result: Specifically, we found that BHP selectively inhibited tumor cell proliferation. Furthermore, BHP enhanced antitumor factor p53 luciferase activity and stimulated expression of p53, p21, and p130 protein. Moreover, we observed that the inhibitory effect of BHP on cell proliferation and premature senescence in a p53-dependent manner. Conclusion: Taken together, we uncovered that BHP may be involved in antitumor suppressor via p53 signaling pathway.

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