UNBS5162 inhibits colon cancer growth via suppression of PI3K/Akt signaling pathway

Colon cancer is a common cause of cancer-related death worldwide. However, the underlying mechanism of tumor progression of colon cancer remains far from being elucidated. In the present study, we report the role of UNBS5162 in colon cancer. UNBS5162 is a naphthalimide that can intercalate into DNA and suppress the expression level of CXCL chemokines. Here, we investigated its effect on cell proliferation, mobility and apoptosis in HCT116 cells, and explored the underlying mechanism. A CCK8 assay revealed that UNBS5162 can block the proliferation of colon cancer cells. Base on a Transwell assay, we showed that cell migration and invasion ability of HCT116 cells are inhibited by UNBS5162. In addition, Annexin V-FITC/PI assay and Western blot analysis were performed to detect whether UNBS5162 could induce cell apoptosis. The results indicated that UNBS5162 increases the number of apoptotic cells remarkably. Furthermore, Western blot analysis demonstrated that UNBS5162 down-regulates the expression level of Bcl2, and up-regulates that of Bax as well as the level of activated Caspase-3. Moreover, we examined the impact of UNBS5162 on PI3K/Akt signaling pathway. UNBS5162 substantially inhibited the phosphorylation of Akt and its downstream effector mTOR, and reduced the expression of p-70. Taken together, these results suggest that UNBS5162 should be considered as a potent therapeutic anticancer agent that targets the PI3K/AKT signaling pathway.

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Cinobufacini Injection Suppresses the Proliferation of Human Osteosarcoma Cells by Inhibiting PI3K/Akt Signaling Pathway

10.21203/rs.3.rs-597951/v1 ◽

2021 ◽

Author(s):

Changbao Chen ◽

Yu Zhai ◽

Yuru Chen ◽

Ye Yuan ◽

Shengyu Hua ◽

...

Keyword(s):

Cell Cycle ◽

Western Blot ◽

Signaling Pathway ◽

Blot Analysis ◽

Akt Signaling ◽

Rna Seq ◽

Akt Signaling Pathway ◽

Cycle Arrest ◽

Mg63 Cells ◽

Cinobufacini Injection

Abstract Background: Cinobufacini injection (CI), an aqueous extraction from the Cutis Bufonis, is broadly used in clinical treatment of cancer in China. However, the underlying molecular mechanisms of CI in treating osteosarcoma (OS) remain unclear. Aberrant activation of PI3K-AKT signaling pathway is the cause of many types of cancer, including OS. Therefore, we investigated the effect of CI on proliferation, apoptosis and cell cycle of OS cells and elucidated the molecular mechanism of CI in inhibiting OS cells. Methods: Cell proliferation of U2OS and MG63 cells after CI treatment was measured by CCK-8 assay, colony formation and morphological changes. Additionally, the cell cycle arrest and apoptosis induced by CI, were determined by FACS and Western blot analysis. The mechanisms of CI on OS were evaluated by RNA-seq and Western blot analysis. Results: We founf that CI reduced the proliferation of U2OS and MG63 cells in a dose- and time- dependent manner. Furthermore, CI induced the U2OS cells cycle arrest in G0/G1 phase, but the MG63 cells cycle arrest in G2/M phase. Consequently, CI triggered the apoptosis in both OS cells, with enhanced caspase-3 activity and decreased expression of Bcl-2/Bax. In addition, RNA-seq data indicated that PI3K-Akt signaling pathway played an essential role in CI treatment. Moreover PI3K and phosphorylation of AKT (p-AKT) were significantly down-regulated by CI in both OS cells. Conclusions: These results indicate that CI significantly inhibited the proliferation, induced the cell cycle arrest, as well as apoptosis in human OS cells, which is mediated by the inactivation of PI3K-Akt signaling pathway. These findings suggest that CI may have potential for the treatment of OS.

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Mytoxin B and Myrothecine A Induce Apoptosis in Human Hepatocarcinoma Cell Line SMMC-7721 via PI3K/Akt Signaling Pathway

Molecules ◽

10.3390/molecules24122291 ◽

2019 ◽

Vol 24 (12) ◽

pp. 2291 ◽

Cited By ~ 1

Author(s):

Huiliang Song ◽

Yi Fu ◽

Dan Wan ◽

Wenjing Xia ◽

Fengwei Lyu ◽

...

Keyword(s):

Western Blot ◽

Cell Line ◽

Blot Analysis ◽

Western Blot Analysis ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Hepatocarcinoma Cell ◽

Apoptotic Protein ◽

Human Hepatocarcinoma Cell Line ◽

Hepatocarcinoma Cell Line

Trichothecene macrolides comprise a class of valuable leading compounds in developing anticancer drugs, however, there are few reports concerning their anticancer mechanisms, especially the anticancer mechanism of the 10,13-cyclotrichothecane derivatives that are found mainly in symbiotic fungi. In vitro anticancer activity of two trichothecene macrolides mytoxin B and myrothecine A against the human hepatocarcinoma cell line SMMC-7721 was investigated in the present study. MTT assay showed that mytoxin B and myrothecine A inhibited the proliferation of SMMC-7721 cells in dose- and time-dependent manners. Annexin V-FITC/PI dual staining assay revealed that mytoxin B and myrothecine A both could induce SMMC-7721 cells apoptosis in a dose-dependent manner. The decreased expression level of anti-apoptotic protein Bcl-2 and the increased expression level of pro-apoptotic protein Bax were observed apparently in Western blot analysis. The reduced ratio of Bcl-2/Bax further confirmed the apoptosis-inducing effect of mytoxin B and myrothecine A on SMMC-7721 cells. Moreover, the expression levels of caspases-3, -8, and -9, and cleaved caspases-3, -8, and -9 were all upregulated in both mytoxin B and myrothecine A-treated cells in Western blot analysis, which indicated that both compounds might induce SMMC-7721 cells apoptosis through not only the death receptor pathway but also the mitochondrial pathway. Finally, mytoxin B and myrothecine A were found to reduce the activity of PI3K/Akt signaling pathway that was similar to the effect of LY294002 (a potent and specific PI3K inhibitor), suggesting that both mytoxin B and myrothecine A might induce SMMC-7721 cells apoptosis via PI3K/Akt pathway.

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Wogonin reverses hypoxia resistance of human colon cancer HCT116 cells via downregulation of HIF-1α and glycolysis, by inhibiting PI3K/Akt signaling pathway

Molecular Carcinogenesis ◽

10.1002/mc.22052 ◽

2013 ◽

Vol 53 (S1) ◽

pp. E107-E118 ◽

Cited By ~ 43

Author(s):

Hu Wang ◽

Li Zhao ◽

Li-Tao Zhu ◽

Yu Wang ◽

Di Pan ◽

...

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Human Colon ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Human Colon Cancer ◽

Hct116 Cells

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Punicalagin Prevents Inflammation in LPS-Induced RAW264.7 Macrophages by Inhibiting FoxO3a/Autophagy Signaling Pathway

Nutrients ◽

10.3390/nu11112794 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2794 ◽

Cited By ~ 8

Author(s):

Cao ◽

Chen ◽

Ren ◽

Zhang ◽

Tan ◽

...

Keyword(s):

Western Blot ◽

Signaling Pathway ◽

Inflammatory Cytokines ◽

Blot Analysis ◽

Western Blot Analysis ◽

Inflammatory Responses ◽

Raw264.7 Macrophages ◽

Tnf Α ◽

Autophagy Inhibition ◽

Pro Inflammatory Cytokines

Punicalagin, a hydrolysable tannin of pomegranate juice, exhibits multiple biological effects, including inhibiting production of pro-inflammatory cytokines in macrophages. Autophagy, an intracellular self-digestion process, has been recently shown to regulate inflammatory responses. In this study, we investigated the anti-inflammatory potential of punicalagin in lipopolysaccharide (LPS) induced RAW264.7 macrophages and uncovered the underlying mechanisms. Punicalagin significantly attenuated, in a concentration-dependent manner, LPS-induced release of NO and decreased pro-inflammatory cytokines TNF-α and IL-6 release at the highest concentration. We found that punicalagin inhibited NF-κB and MAPK activation in LPS-induced RAW264.7 macrophages. Western blot analysis revealed that punicalagin pre-treatment enhanced LC3II, p62 expression, and decreased Beclin1 expression in LPS-induced macrophages. MDC assays were used to determine the autophagic process and the results worked in concert with Western blot analysis. In addition, our observations indicated that LPS-induced releases of NO, TNF-α, and IL-6 were attenuated by treatment with autophagy inhibitor chloroquine, suggesting that autophagy inhibition participated in anti-inflammatory effect. We also found that punicalagin downregulated FoxO3a expression, resulting in autophagy inhibition. Overall these results suggested that punicalagin played an important role in the attenuation of LPS-induced inflammatory responses in RAW264.7 macrophages and that the mechanisms involved downregulation of the FoxO3a/autophagy signaling pathway.

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Gambogic acid protects LPS-induced apoptosis and inflammation in a cell model of neonatal pneumonia through the regulation of TrkA/Akt signaling pathway

BMC Pharmacology and Toxicology ◽

10.1186/s40360-021-00496-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xu Gao ◽

Jingya Dai ◽

Guifang Li ◽

Xinya Dai

Keyword(s):

Western Blot ◽

Signaling Pathway ◽

Cell Model ◽

Akt Signaling ◽

Gambogic Acid ◽

Akt Signaling Pathway ◽

Western Blot Assay ◽

A Cell ◽

Induced Apoptosis ◽

Apoptosis And Inflammation

Abstract Objective In this work, we investigated the effects of gambogic acid (GA) on lipopolysaccharide (LPS)-induced apoptosis and inflammation in a cell model of neonatal pneumonia. Method Human WI-38 cells were maintained in vitro and incubated with various concentrations of GA to examine WI-38 survival. GA-preincubated WI-38 cells were then treated with LPS to investigate the protective effects of GA on LPS-induced death, apoptosis and inflammation. Western blot assay was utilized to analyze the effect of GA on tropomyosin receptor kinase A (TrkA) signaling pathway in LPS-treated WI-38 cells. In addition, human AKT serine/threonine kinase 1 (Akt) gene was knocked down in WI-38 cells to further investigate the associated genetic mechanisms of GA in protecting LPS-induced inflammation and apoptosis. Results Pre-incubating WI-38 cells with low and medium concentrations GA protected LPS-induced cell death, apoptosis and inflammatory protein productions of IL-6 and MCP-1. Using western blot assay, it was demonstrated that GA promoted TrkA phosphorylation and Akt activation in LPS-treated WI-38 cells. Knocking down Akt gene in WI-38 cells showed that GA-associated protections against LPS-induced apoptosis and inflammation were significantly reduced. Conclusions GA protected LPS-induced apoptosis and inflammation, possibly through the activations of TrkA and Akt signaling pathway. This work may broaden our understanding on the molecular mechanisms of human neonatal pneumonia.

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Astragaloside positively regulated osteogenic differentiation of pre-osteoblast MC3T3-E1 through PI3K/Akt signaling pathway

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02690-1 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Wei Bing Jing ◽

Hongjuan Ji ◽

Rui Jiang ◽

Jinlong Wang

Keyword(s):

Western Blot ◽

Osteogenic Differentiation ◽

Real Time ◽

Signaling Pathway ◽

Real Time Pcr ◽

Akt Signaling ◽

Calcium Deposition ◽

Control Group ◽

Akt Signaling Pathway ◽

Western Blot Assay

Abstract Background Osteoporosis is a widespread chronic disease characterized by low bone density. There is currently no gold standard treatment for osteoporosis. The aim of this study was to explore the role and mechanism of Astragaloside on osteogenic differentiation of MC3T3-E1 cells. Methods MC3T3-E1 cells were divided into control and different dose of Astragaloside (10, 20, 40, 50, and 60 μg/ml). Then, ALP and ARS staining were performed to identify the effects of Astragaloside for early and late osteogenic capacity of MC3T3-E1 cells, respectively. Real-time PCR and western blot were performed to assess the ALP, OCN, and OSX expression. PI3K/Akt signaling pathway molecules were then assessed by Western blot. Finally, PI3K inhibitor, LY294002, was implemented to assess the mechanism of Astragaloside in promoting osteogenic differentiation of MC3T3-E1 cells. Results Astragaloside significantly increased the cell viability than the control group. Moreover, Astragaloside enhanced the ALP activity and calcium deposition than the control groups. Compared with the control group, Astragaloside increased the ALP, OCN, and OSX expression in a dose-response manner. Western blot assay further confirmed the real-time PCR results. Astragaloside could significantly increase the p-PI3K and p-Akt expression than the control group. LY294002 partially reversed the promotion effects of Astragaloside on osteogenic differentiation of MC3T3-E1 cells. LY294002 partially reversed the promotion effects of Astragaloside on ALP, OCN, and OSX of MC3T3-E1 cells. Conclusion The present study suggested that Astragaloside promoted osteogenic differentiation of MC3T3-E1 cells through regulating PI3K/Akt signaling pathway.

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Lycopene inhibits growth of human colon cancer cellsvia suppression of the Akt signaling pathway

Molecular Nutrition & Food Research ◽

10.1002/mnfr.200700272 ◽

2008 ◽

Vol 52 (6) ◽

pp. 646-654 ◽

Cited By ~ 69

Author(s):

Feng-Yao Tang ◽

Chung-Jin Shih ◽

Li-Hao Cheng ◽

Hsin-Jung Ho ◽

Hung-Jiun Chen

Keyword(s):

Colon Cancer ◽

Signaling Pathway ◽

Human Colon ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Human Colon Cancer

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LINC00520 targeting miR‐27b‐3p regulates OSMR expression level to promote acute kidney injury development through the PI3K/AKT signaling pathway

Journal of Cellular Physiology ◽

10.1002/jcp.28118 ◽

2019 ◽

Vol 234 (8) ◽

pp. 14221-14233 ◽

Cited By ~ 16

Author(s):

Xinghan Tian ◽

Yongqiang Ji ◽

Yafeng Liang ◽

Jing Zhang ◽

Lina Guan ◽

...

Keyword(s):

Acute Kidney Injury ◽

Signaling Pathway ◽

Kidney Injury ◽

Akt Signaling ◽

Expression Level ◽

Akt Signaling Pathway ◽

Acute Kidney Injury Development

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miR-184 Inhibits Hypertrophic Scar Through Regulating Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Signaling Pathway

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2232 ◽

2020 ◽

Vol 10 (1) ◽

pp. 133-138

Author(s):

Peng Zhao ◽

Junxia Qin ◽

Lili Liang ◽

Xinzhong Zhang

Keyword(s):

Cell Proliferation ◽

Western Blot ◽

Real Time ◽

Signaling Pathway ◽

Real Time Pcr ◽

Hypertrophic Scar ◽

Scar Tissue ◽

Akt Signaling ◽

Scar Formation ◽

Akt Signaling Pathway

Hypertrophic scar (HS) is a process of tissue repair and healing, and excessive fibrosis of local tissue leads to scar formation. During HS formation, fibroblasts (Fb) proliferate, synthesize and secrete and promote HS development. miR-184 regulates skin formation and tissue development. However, miR-184’s role in HS remains unclear. miR-184 expression in HS patients and normal healthy (Control) tissues was measured by real-time PCR. pAKT expression was analyzed by Western blot. Fb cells from human HS were cultured and divided into 2 groups, siRNA NC group and miR-184 siRNA group followed by analysis of miR-184 expression by real time PCR, cell proliferation by MTT assay, secretion of inflammatory factors IL-1β and IL-6 by ELISA, as well as expression of pAKT and AKT by western blot. Compared with control group, miR-184 and pAKT expression was significantly increased in the HS group. Transfection of miR-184 siRNA into Fb significantly downregulated miR-184 expression, inhibited cell proliferation, promoted Caspase 3 activity, decreased IL-1β and IL-6 secretion, and reduced pAKT level (P < 0.05). miR-184 expression is increased in hypertrophic scar tissue. Down-regulation of miR-184 expression in proliferative scar tissue fibroblasts can down-regulate PI3K/AKT signaling pathway, inhibit inflammation, promote apoptosis, inhibit fibroblast proliferation, and regulate hypertrophic scar formation.

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