scholarly journals Compound Prunetin Induces Cell Death in Gastric Cancer Cell with Potent Anti-Proliferative Properties: In Vitro Assay, Molecular Docking, Dynamics, and ADMET Studies

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1086
Author(s):  
Preethi Vetrivel ◽  
Seong Min Kim ◽  
Sang Eun Ha ◽  
Hun Hwan Kim ◽  
Pritam Bhagwan Bhosale ◽  
...  

Gastric cancer is the common type of malignancy positioned at second in mortality rate causing burden worldwide with increasing treatment options. Prunetin (PRU) is an O-methylated flavonoid that belongs to the group of isoflavone executing beneficial activities. In the present study, we investigated the anti-proliferative and cell death effect of the compound PRU in AGS gastric cancer cell line. The in vitro cytotoxic potential of PRU was evaluated and significant proliferation was observed. We identified that the mechanism of cell death was due to necroptosis through double staining and was confirmed by co-treatment with inhibitor necrostatin (Nec-1). We further elucidated the mechanism of action of necroptosis via receptor interacting protein kinase 3 (RIPK3) protein expression and it has been attributed by ROS generation through JNK activation. Furthermore, through computational analysis by molecular docking and dynamics simulation, the efficiency of compound prunetin against RIPK3 binding was validated. In addition, we also briefed the pharmacokinetic properties of the compound by in silico ADMET analysis.

2019 ◽  
Vol 19 (5) ◽  
pp. 610-619 ◽  
Author(s):  
Xue-Qing Zhang ◽  
Lu-Ting Yu ◽  
Pei Du ◽  
Tian-Qi Yin ◽  
Zhi-Yuan Zhang ◽  
...  

Background:Regenerating islet-derived gene family member 4 (Reg4), a well-investigated growth factor in the regenerative pancreas, has recently been reported to be highly associated with a majority of gastrointestinal cancers. Pathological hyper-expression or artificial over-expression of Reg4 causes acceleration of tumor growth, migration, and resistance to chemotherapeutic 5-Fluorouracil (5-FU). Until now, no method has been successfully established for eliminating the effects of Reg4 protein.Methods:This study reports the production of an engineered immunoglobin, a single-chain variable fragment (scFv-Reg4), to specifically bind Reg4 and block the bioactivity. The complementary-determining regions (CDRs) against Reg4 were assigned using MOE and ZDOCK servers. The binding affinity (KD) was determined by bio-layer interferometry (BLI). MKN45 and AGS cell proliferation was determined by Thiazolyl blue tetrazolium bromide (MTT) method and the cell apoptosis was detected by flow cytometry assay.Results:The KD of scFv-Reg4 to Reg4 was determined to be 1.91×10-8. In MKN45 and AGS cell lines, scFv- Reg4 depressed Reg4-stimulated cell proliferation and the inhibitory rates were 27.7±1.5% and 17.3±2.6%, respectively. Furthermore, scFv significantly enhanced 5-FU-induced cell death, from 23.0±1.0% to 28.4±1.2% in MKN45 and 28.2±0.7% to 36.6±0.6% in AGS cells. Treatment with scFv alone could lyse cancer cells to a certain extent, but no significance has been observed.Conclusion:The single-chain antibody (scFv-Reg4) significantly inhibited gastric cancer cell proliferation and synergistically enhanced the lethal effect of 5-FU. Thus, traditional chemo-/radio- therapeutics supplemented with scFv-Reg4 may provide advances in the strategy for gastrointestinal cancer treatment.


2013 ◽  
Vol 7 (1) ◽  
pp. 270-274 ◽  
Author(s):  
JIANFENG ZHANG ◽  
XIAOLING KUAI ◽  
MENGJIAO SONG ◽  
XIAOQI CHEN ◽  
ZHIHUA YU ◽  
...  

2017 ◽  
Vol 42 (1) ◽  
pp. 68-80 ◽  
Author(s):  
Sachie Tanaka ◽  
Hiroaki Miyazaki ◽  
Atsushi Shiozaki ◽  
Daisuke Ichikawa ◽  
Eigo Otsuji ◽  
...  

Background/Aims: Our previous study revealed that cytosolic Cl- affected neurite elongation promoted via assembly of microtubule in rat pheochromocytoma PC12D cells and Cl-–induced blockade of intrinsic GTPase enhanced tubulin polymerization in vitro. Paclitaxel (PTX) is a microtubule-targeted chemotherapeutic drug and stabilizes microtubules resulting in mainly blockade of mitosis at the metaphase-anaphase transition and induction of apoptosis. In the present study, we tried to clarify whether the cytosolic Cl- affected PTX ability to inhibit cell growth in the gastric cancer cell line, MKN28. Methods: To clarify the cytosolic Cl- action on PTX-induced cell death and metaphase-anaphase transition in the gastric cancer cell line, MKN28 cell, and PTX-induced tubulin polymerization, we performed cell proliferation assay, cytosolic Cl- concentration measurement, immunofluorescence microscopy, and in vitro tubulin polymerization assay. Results: The decline of cytosolic Cl- weakened the cytotoxic effect of PTX on cell proliferation of MKN28 cells, which could pass through the metaphase-anaphase transition. Moreover, in vitro PTX-induced tubulin polymerization was diminished under the low Cl- condition. Conclusions: Our results strongly suggest that the upregulation of cytosolic Cl- concentration would enhance the antitumor effect of PTX, and that the cytosolic Cl- would be one of the key targets for anti-cancer therapy.


Author(s):  
Mohammad Mostakhdem Hashemi ◽  
Majid Marjani ◽  
Nahid Poursharifi ◽  
Abdoljalal Marjani

Abstract One of the cancer-related deaths is gastric cancer in this area. Onosma dichroanthum Boiss. roots have been used as an antiseptic and anti-inflammatory for wound healing treatment. The aim of this study was to assess the in vitro cytotoxic and anticancer effects of O. dichroanthum Boiss. roots from the Golestan province of Iran. After identification of the taxonomical effect of O. dichroanthum Boiss., different concentrations of the hydroalcoholic root extract were used. Three different time periods (24, 48, and 72 h) were used to treat AGS gastric cancer and L-929 normal fibroblasts cell lines. The evaluation of different concentrations of root extract was performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The 48 h treatment affected cell survival, while the concentration of 64 μg/mL was determined as IC50 concentrations at 48 h incubation time. The 48 h incubation time with 64 μg/mL showed the best effectiveness on cancerous cell-line while being safe for normal cell-line. Our results show that O. dichroanthum Boiss. roots extract may have cytotoxic and safe effects on gastric cancer cell-line and normal cells in 48 h treatment periods, respectively. The results indicated the O. dichroanthum Boiss. may be as an effective anticancer agent (gastric cancer).


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 34-34
Author(s):  
Jungmin Park

34 Background: To establish NIR optical probe based on the HA-based supramolecular hydrogels (HASHs) conjugated with Cy5.5 for CD44-overexpressed gastric cancer imaging. Methods: To establish HASHs, Cy5.5 NHS ester was conjugated with polyethyleneimine (PEI, 25k Da) and mixed with hyaluronic acid (HA, 1M Da) by an electric interaction. The optimazed ideal molar ratio of PEI to HA was confirmed by DLS and gel electrophoresis. The CD44-expression level for various gastric cancer cell lInes (MKN1, MKN28, MKN45, MKN72, AGS, and N87 cells) was evaluated by FACS analysis. For establishment of the gastric cancer xenograft model, CD44-overexpressed gastric cancer cells were implanted into the BALB/c nude mouse's proximal thigh region. For in vitro targeting study, the cellular affinity of HASHs for CD44-low expressed gastric cancer cell line and CD44-overexpressed gastric cancer cell line was verified by confocal microscopy and IHC staing. For in vivo NIR imaging, HASHs were injected into established xenograft mouse via tail vein and NIR optical imaging was conducted time-dependently. Results: The colloidal size of HASHs was 1.4 micrometer and their morphology was confirmed by electron microscopy. CD44-expression level of MKN45 cells was 92.53% that was higher than MKN28 cells (2.66%). After the treatment of HASHs, the endocytosis into the cytosol was examined for MKN45 cells, but not observed in MKN28 cells due to the deficiency of CD44. 30 days after the transplantion of MKN45 cells, for in vivo imaging study, the prepared HASHs were intraveneously injected into tumor-bearing mouse model. By NIR optical imaging, the optical intensity at tumor site was enhanced upto 3 hours and the maximum intensity was 350 times larger than normal tissue. Conclusions: HASHs was established using supramolecular HA and Cy5.5-conjugated PEI for the targeted imaging of CD44-overexpressed gastric cancer cells. In vitro and in vivo studies demonstrated that SHAHs can visualize the individualized CD44-overexpressed gastric cancer cells by non-invasive optical imaging.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Miaoliang Chen ◽  
Ying Lu ◽  
Ruili Zhang ◽  
Tienan Bi ◽  
Shenkang Zhou

Objective. To study the effects of Huaier polysaccharide SP1 on the proliferation, apoptosis, migration, and invasion of gastric cancer cell line MGC-803 and the underlying mechanism. Methods. MGC-803 cells were cultured in vitro and treated with SP1. The effects of SP1 on the proliferation, apoptosis, migration, and invasion of MGC-803 cells were detected by CCK-8 assay, flow cytometry analysis, and Transwell assay, respectively. Western blot and qRT-PCR were used to detect the expression of related genes. Results. Our study showed that Huaier polysaccharide SP1 could inhibit proliferation, migration, invasion, and promote the apoptosis of MGC-803 cells in vitro in a dose-dependent manner. Huaier polysaccharide SP1 could inhibit the activation of TGF-β/SMAD signal pathway by upregulating SMAD7 expression, thereby downregulating the expression of SOX4, ZEB2, MMP9, Snail, and Slug. Conclusion. Huaier polysaccharide SP1 can regulate the proliferation, apoptosis, migration, and invasion of gastric cancer cells by promoting the expression of SMAD7 and inhibiting the activation of TGF-β/SMAD signal pathway as well as the expression of the downstream oncogenes.


1994 ◽  
Vol 161 (3) ◽  
pp. 519-525 ◽  
Author(s):  
Richard J. Bold ◽  
Patrick S. Lowry ◽  
Jin Ishizuka ◽  
James F. Battey ◽  
Courtney M. Townsend ◽  
...  

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