ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner

Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.

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Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22115792 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5792

Author(s):

Laura Francesca Pisani ◽

Gian Eugenio Tontini ◽

Carmine Gentile ◽

Beatrice Marinoni ◽

Isabella Teani ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Line ◽

Cell Lines ◽

Gene Expression Regulation ◽

Gastric Epithelium ◽

Cell Cycle Gene ◽

Dependent Manner

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.

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Inactivation of the Akt/FOXM1 Signaling Pathway by Panobinostat Suppresses the Proliferation and Metastasis of Gastric Cancer Cells

International Journal of Molecular Sciences ◽

10.3390/ijms22115955 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5955

Author(s):

Na-Ri Lee ◽

Da-Yeah Kim ◽

Hua Jin ◽

Ruoyu Meng ◽

Ok Hee Chae ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Animal Experiments ◽

Hdac Inhibitors ◽

Dependent Manner ◽

Akt Inhibitor ◽

M Cell ◽

Gastric Cancer Cells ◽

Protein Levels

Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. Histone deacetylase (HDAC) inhibitors are a new class of cytostatic agents available for the treatment of various cancers and diseases. Although numerous clinical and pre-clinical trials on the anticancer effects of panobinostat have been conducted, only a few reports have investigated its efficacy in gastric cancer. The present study aimed to investigate the effects of panobinostat in gastric cancer cells. Panobinostat significantly inhibited the cell viability and proliferation of the gastric cancer cell lines SNU484 and SNU638 in a dose-dependent manner; it reduced the colony-forming ability of these cells. Moreover, it induced apoptosis as indicated by increased protein levels of cleaved poly ADP-ribose polymerase and cleaved caspase-3. Panobinostat induced the G2/M cell cycle arrest in SNU484 and SNU638 cells and subsequently decreased the G2/M phase regulatory-associated protein expression of p-Wee1, Myt1, and Cdc2. Furthermore, panobinostat significantly inhibited the metastasis of SNU484 and SNU638 cells by regulating the expression of MMP-9 and E-cadherin. Further, it decreased the protein levels of p-Akt and forkhead box protein M1 (FOXM1). These effects were reversed by the Akt agonist SC79 and were accelerated by the Akt inhibitor LY2940002. Moreover, tumor growth in xenograft animal experiments was suppressed by panobinostat. These results indicated that panobinostat inhibits the proliferation, metastasis, and cell cycle progression of gastric cancer cells by promoting apoptosis and inactivating Akt/FOXM1 signaling. Cumulatively, our present study suggests that panobinostat is a potential drug for the treatment of gastric cancer.

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Naturally occurring aesculetin coumarin exerts antiproliferative effects in gastric cancer cells mediated via apoptotic cell death, cell cycle arrest and targeting PI3K/AKT/M-TOR signalling pathway

Acta Biochimica Polonica ◽

10.18388/abp.2020_5463 ◽

2021 ◽

Author(s):

Jie Zhang ◽

Min Feng ◽

Wenxian Guan

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Death ◽

Apoptotic Cell ◽

Signalling Pathway ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Antiproliferative Effects ◽

Cycle Arrest ◽

M Phase

Aesculetin is an active member of coumarins that has been reported to possess significant medicinal and biological importance. It has also been shown with potential anticancer activity against different human cancers including breast, lung and hepatocellular carcinoma. Therefore, the current investigation was undertaken to examine the anticancer effects of aesculetin against gastric cancer. MTT assay was performed to check the cellular viability and clonogenic assay was executed to assess the effect of aesculetin on colony formation capacity of SGC-7901 gastric cancer cells. Apoptosis was analysed by AO/EB staining and annexin V-FITC/PI staining assays. Cell cycle phases were monitored using flowcytometry and western blotting was used to detect the effects of aesculetin on PI3K/AKT/M-TOR signalling pathway. Results indicated that aesculetin not only reduced the cellular proliferation in time-dependent manner but dose-dependent manner as well. Clonogenic tendency of SGC-7901 cells was retarded significantly by the aesculetin. The antiproliferative effects of aesculetin may arbitrate via apoptosis. Further, flow cytometric analysis revealed that the G2/M-phase SGC-7901 cells amplified number with increasing aesculetin doses. Indicating blocking of cell cycle at G2/M-phase. Finally, western blotting assay suggested blocking of PI3K/AKT/M-TOR signalling pathway by aesculetin in gastric cancer SGC-7901 cells. Taking altogether, aesculetin could induce significant growth inhibitory effects against gastric cancer SGC-7901 cells. Moreover, aesculetin could induce apoptotic cell death, cell cycle arrest and block PI3K/AKT/M-TOR signalling pathway.

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Sulforaphane induces S-phase arrest and apoptosis via p53-dependent manner in gastric cancer cells

Scientific Reports ◽

10.1038/s41598-021-81815-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yuan Wang ◽

Huazhang Wu ◽

Nannan Dong ◽

Xu Su ◽

Mingxiu Duan ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Western Blot ◽

Cell Apoptosis ◽

S Phase ◽

Phase Cell ◽

Dependent Manner ◽

Gastric Cancer Cells ◽

Dose Dependent

AbstractSulforaphane (SFN) extracted from broccoli sprout has previously been investigated for its potential properties in cancers, however, the underlying mechanisms of the anticancer activity of SFN remain not fully understood. In the present study, we investigate the effects of SFN on cell proliferation, cell cycle, cell apoptosis, and also the expression of several cell cycle and apoptosis-related genes by MTT assay, flow cytometry and western blot analysis in gastric cancer (GC) cells. The results showed that SFN could impair the colony-forming ability in BGC-823 and MGC-803 cell lines compared with the control. In addition, SFN significantly suppressed cell proliferation by arresting the cell cycle at the S phase and enhancing cell apoptosis in GC cells in a dose-dependent manner. Western blot results showed that SFN treatment significantly increased the expression levels of p53, p21 and decreased CDK2 expression, which directly regulated the S phase transition. The Bax and cleaved-caspase-3 genes involved in apoptosis executive functions were significantly increased in a dose-dependent manner in BGC-823 and MGC-803 cells. These results suggested that SFN-induced S phase cell cycle arrest and apoptosis through p53-dependent manner in GC cells, which suggested that SFN has a potential therapeutic application in the treatment and prevention of GC.

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Effect of Chrysanthemum flavonoids on growth and cell cycle regulators of gastric cancer cell

Cell Biology International ◽

10.1042/cbi034s050d ◽

2010 ◽

Vol 34 (8) ◽

pp. S50-S50

Author(s):

Xiaoyan Pan ◽

Xinmei Zhou ◽

Guangtao Xu ◽

Lingfen Miao ◽

Shuoru Zhu

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cell ◽

Gastric Cancer Cell ◽

Cell Cycle Regulators

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Faculty Opinions recommendation of Effect of p27(KIP1) on cell cycle and apoptosis in gastric cancer cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1031750.367857 ◽

2006 ◽

Author(s):

Esther Bullitt

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Gastric Cancer Cells ◽

P27 Kip1

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OSI-027 alleviates oxaliplatin chemoresistance in gastric cancer cells by suppressing P-gp induction

Current Molecular Medicine ◽

10.2174/1566524020666201120113538 ◽

2020 ◽

Vol 20 ◽

Author(s):

En Xu ◽

Hao Zhu ◽

Feng Wang ◽

Ji Miao ◽

Shangce Du ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Mammalian Target Of Rapamycin ◽

Cell Counting ◽

Gastric Cancer Cells ◽

Ags Cells ◽

Dual Inhibitor ◽

Induced Apoptosis

: Gastric cancer is one of the most common malignancies worldwide and the third leading cause of cancer-related death. In the present study, we investigated the potential activity of OSI-027, a potent and selective mammalian target of rapamycin complex 1/2 (mTOR1/2) dual inhibitor, alone or in combination with oxaliplatin against gastric cancer cells in vitro. Cell counting kit-8 assays and EdU staining were performed to examine the proliferation of cancer cells. Cell cycle and apoptosis were detected by flow cytometry. Western blot was used to detect the elements of the mTOR pathway and Pgp in gastric cancer cell lines. OSI-027 inhibited the proliferation of MKN-45 and AGS cells by arresting the cell cycle in the G0/G1 phase. At the molecular level, OSI-027 simultaneously blocked mTORC1 and mTORC2 activation, and resulted in the downregulation of phosphor-Akt, phpspho-p70S6k, phosphor-4EBP1, cyclin D1, and cyclin-dependent kinase4 (CDK4). Additionally, OSI-027 also downregulated P-gp, which enhanced oxaliplatin-induced apoptosis and suppressed multidrug resistance. Moreover, OSI-027 exhibited synergistic cytotoxic effects with oxaliplatin in vitro, while a P-gp siRNA knockdown significantly inhibited the synergistic effect. In summary, our results suggest that dual mTORC1/mTORC2 inhibitors (e.g., OSI-027) should be further investigated as a potential valuable treatment for gastric cancer.

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Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200203160117 ◽

2020 ◽

Vol 20 (6) ◽

pp. 734-750

Author(s):

Wallax A.S. Ferreira ◽

Rommel R. Burbano ◽

Claudia do Ó. Pessoa ◽

Maria L. Harada ◽

Bárbara do Nascimento Borges ◽

...

Keyword(s):

Cell Cycle ◽

Cell Cycle Arrest ◽

Signaling Pathway ◽

Glioma Cell ◽

Molecular Mechanisms ◽

Glioma Cells ◽

Dependent Manner ◽

M Cell ◽

Trypan Blue Exclusion ◽

Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

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