MiR-144-3p targets STC1 to activate PI3K/AKT pathway to induce cell apoptosis and cell cycle arrest in selenium deficiency broilers

Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. Ginsenosides exhibit anticancer activity against various cancer cells. However, the effects of ginsenoside Rh1 on BC and the underlying mechanisms remain unknown. Here, we investigated the anticancer effects of Rh1 on human BC MCF-7 and HCC1428 cells and the underlying signaling pathways. The anticancer effects of Rh1 in vitro were evaluated using sulforhodamine B (SRB), 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), clonogenic assay, propidium iodide (PI)/Hoechst staining, Western blotting, flow cytometry, and immunofluorescence analysis. The in vivo effects of Rh1 were determined using a xenograft model via hematoxylin and eosin and the immunohistochemistry staining of tumor tissues. We found that Rh1 exerted cytotoxicity in the cells by increasing cell apoptosis, autophagy, and cell cycle arrest. These effects were further enhanced by a phosphatidylinositol 3-kinase (PI3K) inhibitor but were rescued by the inhibition of reactive oxygen species (ROS). Moreover, enhanced ROS generation by Rh1 inhibited the activation of the PI3K/Akt pathway. Consistently, Rh1 treatment significantly reduced tumor growth in vivo and increased the ROS production and protein expression of LC3B and cleaved caspase-3 but decreased the phosphorylation of Akt and retinoblastoma (Rb) in tumor tissues. Taken together, Rh1 exerted a potential anticancer effect on BC cells by inducing cell cycle arrest, apoptosis, and autophagy via inhibition of the ROS-mediated PI3K/Akt pathway.

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PTENInhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERTPathway in Lung Adenocarcinoma A549 Cells

BioMed Research International ◽

10.1155/2016/2476842 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 31

Author(s):

Xiao-Xiao Lu ◽

Lan-Yu Cao ◽

Xi Chen ◽

Jian Xiao ◽

Yong Zou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Lung Adenocarcinoma ◽

Cell Cycle Arrest ◽

Cell Apoptosis ◽

A549 Cells ◽

Akt Pathway ◽

Wild Type ◽

Cycle Arrest ◽

Lung Adenocarcinoma A549

PTENplays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role ofPTENin lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutantPTENas well as A549 cells expressing a siRNA directed toward endogenousPTEN. Overexpression of wild-typePTENprofoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase proteinhTERT. In contrast, in cells expressing aPTENdirected siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, andhTERTprotein expression were observed. A549 cells transfected with aPTENmutant lacking phosphatase activity (PTEN-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects ofPTEN. Taken together, we have demonstrated thatPTENdownregulates the PI3K/AKT/hTERTpathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.

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Polyphyllin I Induces Cell Cycle Arrest and Cell Apoptosis in Human Retinoblastoma Y-79 Cells through Targeting p53

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180108095148 ◽

2018 ◽

Vol 18 (6) ◽

pp. 875-881 ◽

Cited By ~ 7

Author(s):

Xue Zhu ◽

Ke Wang ◽

Kai Zhang ◽

Yi Pan ◽

Fanfan Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Cell Apoptosis ◽

Potential Effect ◽

External Beam Radiation ◽

Beam Radiation ◽

P53 Expression ◽

Cycle Arrest ◽

Wide Range ◽

Human Retinoblastoma

Background: Retinoblastoma is the most common intraocular malignant tumor in childhood. Although external beam radiation and enucleation are effective to control retinoblastoma, eye salvage and vision preservation are still significant challenges. Polyphyllin I (PPI), a natural compound extracted from Paris polyphylla rhizomes, has a wide range of activities against many types of cancers. However, the potential effect of this herbal compound on retinoblastoma has not yet been investigated. Method: In the present study, we evaluated the cytotoxic effect of PPI on human retinoblastoma Y-79 cells as well as its underlying molecular mechanism. Our results indicated that PPI treatment significantly inhibited cell proliferation, arrested the cell cycle at G2/M phase and induced cell apoptosis of Y79 cells through the mitochondrial- dependent intrinsic pathway. Moreover, p53 is involved in PPI-induced cytotoxicity in human retinoblastoma Y-79 cells. Exposure to 10 μM PPI for 48 h dramatically induced the expression levels of p53, phosphorylated- p53 and acetylated-p53. Furthermore, blockade of p53 expression effectively attenuated PPI-induced cell cycle arrest and cell apoptosis in Y-79 cells. Result: These results demonstrated that PPI exhibits anti-proliferation effect on human retinoblastoma Y-79 cells through modulating p53 expression, stabilization and activation. This information shed light on the potential application of PPI in retinoblastoma therapy.

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