Effects and mechanism of GA-13315 on the proliferation and apoptosis of KB cells in oral cancer

Shen, Shuai; Tang, Jing

doi:10.3892/ol.2017.6279

Cited by 8 publications

(11 citation statements)

References 14 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…cell proliferation, with or without Ga-13315 treatment, was measured using a cell Counting Kit-8 (CCK-8) assay kit (BD Biosciences). Briefly, cells were seeded into 96-well plates at 2,000 cells/plate, incubated overnight and treated with various doses (4,8,16 and 32 ng/µl) of Ga-13315 or the vehicle control for 48 h. Then, 10 µl ccK8 solution was added to each well and cells were incubated for an additional 2.5 h. optical density was measured by a microplate reader (Thermo Fisher Scientific, inc.) at a wavelength of 450 nm.…”

Section: Methodsmentioning

confidence: 99%

“…in GA-13315-treated lung cancer cells cassette subfamily B member 1 (7). it inhibited proliferation and caused apoptosis in oral cancer (8). The product of the protein phosphatase 2 regulatory subunit Bbeta (PPP2r2B) gene belongs to the phosphatase ii regulation subunit B family, which serves important roles in cell growth and division (9).…”

Section: Trim67 Promotes Nf-κb Pathway and Cell Apoptosismentioning

confidence: 99%

“…PPP2r2B methylation is associated with survival and prognosis in patients with gliomas (10). Ga-13315 also suppressed PPP2r2B expression in H1299 lung cancer cells (8). In vivo studies have indicated that it had a significant inhibitory effect on the growth of human colon cancer xenografts in HcT116 nude mice without causing any apparent side effects (6).…”

Section: Trim67 Promotes Nf-κb Pathway and Cell Apoptosismentioning

confidence: 99%

See 2 more Smart Citations

TRIM67 promotes NF‑κB pathway and cell apoptosis in GA‑13315‑treated lung cancer cells

et al. 2019

View full text Add to dashboard Cite

13-chlorine-3,15-dioxy-gibberellic acid methyl ester (Ga-13315), a gibberellin derivative, possesses strong anti-tumor activity in vitro and in vivo. The present study aimed to investigate the underlying mechanisms of Ga-13315-induced apoptosis in human non-small cell lung cancer cell lines. lung cancer cells were treated with different doses of Ga-13315 (4, 8, 16 and 32 ng/µl) for 48 h, and a ccK8 assay was performed to measure cell viability. alteration in gene expression was identified using rna-sequencing (rna-Seq). Quantitative polymerase chain reaction (qPcr) was used to confirm the differentially expressed genes (DEGs) identified in RNA-Seq. Gene expression plasmids or small interfering rna were used to overexpress or silence targeted genes, in order to investigate downstream signals. chromatin immunoprecipitation was conducted to evaluate the binding of transcription factors to the target genes. a Student's t-test or one-way analysis of variance followed by Tukey's honestly significant difference post-hoc test were performed to evaluate the significance between groups. P<0.05 was considered to indicate a statistically significant difference. GA-13315 significantly decreased the number of viable cells and induced apoptosis among lung cancer cells (median lethal dose =12-16 ng/µl). RNA-Seq identified 250 significant deGs, including 94 upregulated and 156 downregulated genes in A549 cells (P<0.05; fold change ≥1.5). Upregulation of TriM67, nF-κB subunit 2 (nF-κB2) and FaS was additionally confirmed using qPCR and western blot analysis in A549 and H460 cells. Apoptosis of A549 cells was significantly decreased following knockdown of TriM67. Ga-13315 promoted TriM67 expression to increase FaS expression and cell apoptosis. TriM67 promoted the processing of nF-κB2 into its active form, p52, which then enhanced the nF-κB pathway and Ga-13315-induced apoptosis.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Trim67 Promotes Nf-κb Pathway and Cell Apoptosismentioning

confidence: 99%

Section: Trim67 Promotes Nf-κb Pathway and Cell Apoptosismentioning

confidence: 99%

See 1 more Smart Citation

TRIM67 promotes NF‑κB pathway and cell apoptosis in GA‑13315‑treated lung cancer cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Our previous study demonstrated the inhibitory effect of GA-13315 on proliferation of A549 cells in xenograft mice models [12]. In addition, more recent evidence revealed that GA-13315 inhibited the growth and proliferation of oral, breast, and leukemia tumor cells through exerting antiangiogenic activity [12, 14], and the value of inhibitory concentration 50 (IC 50 ) in various tumor cell lines ranged from 0.13 to 30.28 μg/ml. However, the antitumor effect and the underlying mechanism of GA-13315 on human lung adenocarcinoma have not been fully evaluated.…”

Section: Introductionmentioning

confidence: 99%

Anti-tumor effects and mechanism of GA-13315, a novel gibberellin derivative, in human lung adenocarcinoma: an in vitro and in vivo study

et al. 2019

View full text Add to dashboard Cite

ObjectiveTo investigate the anti-tumor effects and the mechanism of the compound 13-chlorine-3, 15-dioxy-gibberellic acid methyl ester (GA-13315) in lung adenocarcinoma in vitro and in vivo.MethodsThe antiproliferative effect of GA-13313 on the A549 cell line was determined by MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide) assay. A xenograft model of A549 was established to evaluate the anti-tumor effect and histopathological examination was performed to assess the toxicity of GA-13315. Apoptosis was detected by TUNEL staining in tissues and flow cytometry in cells; activation of caspase-3, caspase-8 and caspase-9 was evaluated by immunohistochemical analysis; protein levels of Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), caspase-4, activating transcription factor 4 (ATF4), glucose-regulated protein 78 (GRP78) and growth arrest and DNA damage-inducible gene 153 (GADD153) were determined by western blotting. Mitochondrial membrane potential (MMP) was measured by the JC-1 fluorescence probe.ResultsOur results showed that GA-13315 exhibited potent, dose- and time-dependent anti-proliferative activity, and the IC50 values were 37.43 ± 2.73, 28.08 ± 7.76 and 19.29 ± 7.61 μM at 24, 48, and 72 h, respectively. The xenograft experiment revealed that tumor weight and volume were significantly decreased after GA-13315 3 mg/kg and 9 mg/kg (P < 0.05) treatment, and GA-13315 had low toxicity in bone marrow, kidney and colon tissues. GA-13315 triggered remarkable apoptosis in A549 cells at the concentration of 25.6 μM and 32 μM (P < 0.05) and activated caspase-3, − 8 and − 9. Moreover, GA-13315 induced apoptosis through the mitochondrial apoptosis pathway by elevating the Bax/Bcl-2 ratio, releasing cytochrome c and activating caspase-9 in A549 cells. In the endoplasmic reticulum apoptosis pathway, the levels of caspase-4, ATF4, GRP78 and GADD153 were markedly upregulated.ConclusionsThis study suggests that GA-13315 can be considered as a promising chemotherapeutic agent with anticancer activity in treatment of lung cancer in future.

show abstract

“…It inhibits the growth and also accelerates the apoptosis of KB oral cancer cells. GA-13315 also possesses anti-angiogenic properties [77,78].…”

mentioning

confidence: 99%

The Structure-Based Virtual Screening for Natural Compounds that Bind with the Activating Receptors of Natural Killer Cells

Rowaiye¹,

Oni

Uzochukwu

et al. 2020

Preprint

View full text Add to dashboard Cite

Aim: This study is aimed at prospecting for natural compounds that have strong binding affinity for the Activating Receptors of Natural Killer (NK) cells.Background: NK cells are responsible for the immunosurveillance of tumor and virally-infected cells. The cytotoxic potentials of this unique population of immune cells are triggered by the activating receptors. Through ligand-binding, these receptors induce the tyrosine phosphorylation of adapter proteins through their Immunoreceptor Tyrosine-based Activation Motif ITAM sequences and this triggers direct cytotoxicity and the production of cytokines through different signal pathways.Objective: To computationally predict the selectivity, specificity, and efficacy of natural compounds to be used as immunostimulatory agents for cancer treatment. Method:In this study, 1,697 natural compounds were obtained from 82 edible tropical plants through data mining. The molecular docking simulations of these compounds were executed against 18 activating NK cells receptor targets using the Python Prescription 0.8. An arbitrary docking score ≥ -7.0 kcal/mol was chosen as cut off value. Further screening for oral bioavailability, promiscuity, molecular complexity and pharmacokinetic properties using the Swissadme and pkCSM webservers. The ligand similarity analysis and phylogenetic analysis of the receptors was carried out with the ChemMine and Clustal Omega webservers respectively. Binding site analyses and bioactivity prediction were also done with the Protein-Ligand Interaction Profiler and Molinspiration webservers respectively. Normal mode analyses were carried out with the CABS-flex 2.0 server.Result: Seventeen bioactive and non-promiscuous lead compounds with good physicochemical and pharmacokinetic properties were identified. Conclusion:Further tests are required to evaluate the efficacy of the lead compounds.Cancer is a group of diseases characterized by erratic cell growth which invade and spread into other parts of the body [1,2]. They are caused by DNA damage and an ineffective DNA repair mechanism.According to a 2015 WHO report, Cancer is the second leading cause of death globally and there were 90.5 million incidences of cancer in 2015 which accounted for 8.8 million deaths [3].Cancers are caused by a persistent damage to DNA which culminates into mutations of certain gene sequences in the human genome [4]. Expression of these mutant sequences lead to an autonomous and unregulated hyper-proliferation of cells; insufficient apoptosis; altered differentiation and metabolism; genomic instability and immortalization [5]. The abnormal proliferation of cells is due to alterations in the cell cycle replication mechanism due to nuclear and cytoplasm distortions. These changes include hyperchromatism, increased telomerase expression, prominent nucleoli, irregular chromatin distribution within nuclei, and increased size of nucleus, pleomorphism, and chromosomal translocations [6,7].Available cancer therapies such as chemotherapy are non-selective as other normal rapidly divid...

show abstract

Effects and mechanism of GA-13315 on the proliferation and apoptosis of KB cells in oral cancer

Cited by 8 publications

References 14 publications

TRIM67 promotes NF‑κB pathway and cell apoptosis in GA‑13315‑treated lung cancer cells

TRIM67 promotes NF‑κB pathway and cell apoptosis in GA‑13315‑treated lung cancer cells

Anti-tumor effects and mechanism of GA-13315, a novel gibberellin derivative, in human lung adenocarcinoma: an in vitro and in vivo study

The Structure-Based Virtual Screening for Natural Compounds that Bind with the Activating Receptors of Natural Killer Cells

Contact Info

Product

Resources

About