SW480 Cell Lines Research Articles

Identification of 2,4-Di-tert-butylphenol (2,4-DTBP) as the Major Contributor of Anti-colon cancer Activity of Active Chromatographic Fraction of Parkia javanica (Lamk.) Merr. Bark Extract

Parkia javanica (Lamk.) Merr. is an ethnomedicinal leguminous plant species from northeastern India with a long history of medicinal use among various tribes of this region to treat cholera, dysentery, stomach aches, diarrhea and food poisoning, having antibacterial, wound-healing, anticancer and anti-inflammatory properties. Therefore, in this current study, the methanolic bark extract was carried out and fractionated by using flash chromatography, examined the cytotoxicity of the respective fractions on colon cancer cell lines, and evaluated the major phytochemical compounds present in the fractions using Gas Chromatography-Mass Spectrometry (GC-MS) chemical profiling. Chemical profiling of the fractions by GC-MS revealed in fraction-1 and -2, 2,4-Di-tert-butylphenol was the major compound (50.740% in fraction-1, 21.277% in fraction-2, and 7.859% in fraction-3) having reported anticancer activity. The gradation of the presence of this compound in the fractions was corroborated by the gradation of anti-colon cancer activity of the respective fractions on both the colon carcinoma cell lines. However, the presence of D-Allose in a substantial amount (20.870%) in only fraction-3 could not increase the anticancer activity of fraction-3 over the other two fractions. An in vitro cytotoxic assay guided evaluation of three flash chromatographic fractions (fraction-1, -2, and -3) of methanolic extract of Parkia javanica bark showed significant anticancer properties on two human colon carcinoma cell lines (HCT116 and SW480). The order of efficacy of the fractions was fraction-1> fraction-2 > fraction-3. In a time and dose-dependent experiment, fraction-1, being the most active one, showed an IC50 value of 16.25 µgml-1 (24 hrs), 9.94 µgml-1 (48 hrs), and 9.38 µgml-1 (72 hrs) on HCT116 and 35 µgml-1 (24 hrs), 20.14 µgml-1 (48 hrs), and 19.71 µgml-1 (72 hrs) on the SW480 cell line. Parkia javanica bark extract is bestowed with the potential of anti-colon cancer property and upon chemical profiling of different chromatographic fractions of the extract, 2,4-Di-tert-butylphenol has been identified as the primary anticancer component of the extract.

DTX2 overexpression promotes migration and invasion of colorectal cancer cells through the Notch2/Akt axis

To investigate the effect of changes in DTX2 expression level on migration and invasion of colorectal cancer (CRC) cells and explore the mechanism. Two CRC cell lines SW620 and LoVo were transfected with a specific shRNA targeting DTX2 (DTX2-shRNA) or a DTX2-overexpressing plasmid (pcDNA-DTX2), and the transfection efficiency was evaluated with RT-qPCR and Western blotting. Scratch and Transwell assays were used to assess the changes in migration and invasion ability of the transfected cells, and the cellular expression levels of Notch2, NICD, AKT, p-Akt and MMP-2/9 proteins were detected with Western blotting. The CRC cells were co-transfected with pcDNA-DTX2 and Notch2 siRNA to assess the effect of Notch2 knockdown on DTX2 overexpression-induced enhancement of cell migration and invasion. The expression levels of DTX2 at both the mRNA and protein levels were significantly decreased in CRC cells transfected with DTX2- shRNA (P < 0.01) and increased in cells transfected with pcDNA-DTX2 (P < 0.01). Scratch and Transwell assays showed that the migration and invasion abilities of CRC cells were significantly lowered following DTX2 knockdown (P < 0.01) and were enhanced in cells with DTX2 overexpression (P < 0.01). The expression levels of Notch2, NICD, p-Akt and MMP-2 proteins decreased significantly in CRC cells with DTX2 knockdown (P < 0.05) and increased obviously in DTX2-overexpressing cells (P < 0.05). In both of the two CRC cell lines, transfection with Notch2 siRNA obviously reversed the effect of DTX2 overexpression in promoting cell migration and invasion (P < 0.01) and expressions of the related proteins. DTX2 overexpression promotes migration and invasion of CRC cells through the Notch2/Akt axis, suggesting the potential of DTX2 as a new biological indicator of CRC.

Metformin and thymoquinone co-treatment enhance 5-fluorouracil cytotoxicity by suppressing the PI3K/mTOR/HIF1α pathway and increasing oxidative stress in colon cancer cells.

This study investigated the chemotherapeutic effects of 5-fluorouracil (5-FU), metformin (Met), and/or thymoquinone (TQ) single/dual/triple therapies in the HT29, SW480 and SW620 colon cancer (CRC) cell lines. Cell cycle/apoptosis were measured by flow cytometry. The gene and protein expression of apoptosis (PCNA/survivin/BAX/Cytochrome-C/Caspase-3) and cell cycle (CCND1/CCND3/p21/p27) molecules, the PI3K/mTOR/HIF1α oncogenic pathway, and glycolysis regulatory enzymes were measured by quantitative-PCR and Western blot. Markers of oxidative stress were also measured by colorimetric assays. Although all treatments induced anti-cancer effects related to cell cycle arrest and apoptosis, the triple therapy showed the highest pro-apoptotic actions that coincided with the lowest expression of CCND1/CCND3/PCNA/survivin and the maximal increases in p21/p27/BAX/Cytochrome-C/Caspase-3 in all cell lines. The triple therapy also revealed the best suppression of the PI3K/mTOR/HIF1α pathway by increasing its endogenous inhibitors (PTEN/AMPKα) in all cell lines. Moreover, the lowest expression of lactate dehydrogenase and pyruvate dehydrogenase kinase-1 with the highest expression of pyruvate dehydrogenase were seen with the triple therapy, which also showed the highest increases in oxidative stress markers (ROS/RNS/MDA/protein carbonyl groups) alongside the lowest antioxidant levels (GSH/CAT) in all cell lines. In conclusion, this is the first study to reveal enhanced anti-cancer effects for metformin/thymoquinone in CRC that were superior to all monotherapies and the other dual therapies. However, the triple therapy approach showed the best tumoricidal actions related to cell cycle arrest and apoptosis in all cell lines, possibly by enhancing oxidative glycolysis and augmenting oxidative stress through stronger modulation of the PI3K/mTOR/HIF1α oncogenic network.

Secretory Factors from Calcium-Sensing Receptor-Activated SW872 Pre-Adipocytes Induce Cellular Senescence and A Mitochondrial Fragmentation-Mediated Inflammatory Response in HepG2 Cells

Adipose tissue inflammation in obesity has a deleterious impact on organs such as the liver, ultimately leading to their dysfunction. We have previously shown that activation of the calcium-sensing receptor (CaSR) in pre-adipocytes induces TNF-α and IL-1β expression and secretion; however, it is unknown whether these factors promote hepatocyte alterations, particularly promoting cell senescence and/or mitochondrial dysfunction. We generated conditioned medium (CM) from the pre-adipocyte cell line SW872 treated with either vehicle (CMveh) or the CaSR activator cinacalcet 2 µM (CMcin), in the absence or presence of the CaSR inhibitor calhex 231 10 µM (CMcin+cal). HepG2 cells were cultured with these CM for 120 h and then assessed for cell senescence and mitochondrial dysfunction. CMcin-treated cells showed increased SA-β-GAL staining, which was absent in TNF-α- and IL-1β-depleted CM. Compared to CMveh, CMcin arrested cell cycle, increased IL-1β and CCL2 mRNA, and induced p16 and p53 senescence markers, which was prevented by CMcin+cal. Crucial proteins for mitochondrial function, PGC-1α and OPA1, were decreased with CMcin treatment, concomitant with fragmentation of the mitochondrial network and decreased mitochondrial transmembrane potential. We conclude that pro-inflammatory cytokines TNF-α and IL-1β secreted by SW872 cells after CaSR activation promote cell senescence and mitochondrial dysfunction, which is mediated by mitochondrial fragmentation in HepG2 cells and whose effects were reversed with Mdivi-1. This investigation provides new evidence about the deleterious CaSR-induced communication between pre-adipocytes and liver cells, incorporating the mechanisms involved in cellular senescence.

ESM1 promotes angiogenesis in colorectal cancer by activating PI3K/Akt/mTOR pathway, thus accelerating tumor progression.

This study aimed to explore the influence of endothelial cell-specific molecule 1 (ESM1) expression on colorectal cancer (CRC) cells and preliminarily analyze its possible mechanism, so as to lay a foundation for research about potential biological targets of CRC. First, CRC cells were transfected with ESM1-negative control (NC), ESM1-mimic and ESM1-inhibitor and randomly assigned to ESM1-NC group, ESM1-mimic group and ESM1-inhibitor group, respectively. Then the cells were harvested at 48 h after transfection for subsequent experiments. The results manifested that after up-regulation of ESM1, the distance of CRC SW480 and SW620 cell lines migrating to the scratch center rose notably, and the number of migrating cells, basement membrane-penetrating cells, colonies formed and angiogenesis was increased overtly, indicating that ESM1 overexpression can promote tumor angiogenesis in CRC and accelerate tumor progression. Combined with results of bioinformatics analysis, the molecular mechanism by which ESM1 promoted tumor angiogenesis in CRC and accelerated tumor progression was explored through suppressing the protein expression of phosphatidylinositol 3-kinase (PI3K). Western blotting revealed that after intervention with PI3K inhibitor, the protein expressions of phosphorylated PI3K (p-PI3K), phosphorylated protein kinase B (p-Akt) and phosphorylated mammalian target of rapamycin (p-mTOR) were decreased evidently, and the protein expressions of matrix metalloproteinase-2 (MMP-2), MMP-3, MMP-9, Cyclin D1, Cyclin A2, VEGF, COX-2 and HIF-1α subsequently declined. ESM1 may promote angiogenesis in CRC by activating the PI3K/Akt/mTOR pathway, thus accelerating tumor progression.

Fangchinoline Exerts Anticancer Effects on Colorectal Cancer Cells by Evoking Cell Apoptosis via Endoplasmic Reticulum Stress.

We studied the anti-tumor effect of fangchinoline (FAN) against human colorectal cancer cell lines CCL-244 and SW480 and analyzed the mechanism of FAN action. The cell viability and apoptosis were assessed by MTT test and Annexin V-PI staining; caspase-3 activity was measured by Western blotting. The expression of endoplasmic reticulum stress-related proteins was assessed by real-time PCR, Western blotting, and gene transfection. It was found that FAN inhibited cell growth and induced apoptosis in human colorectal cancer cell lines CCL-244 and SW480 in a dose-dependent manner. The caspase-3 inhibitor Ac-DEVD-CHO could reverse the inhibitory effect of FAN. Moreover, FAN significantly increased the expression of endoplasmic reticulum stress-related proteins p-PERK, p-eIF2α, ATF4, and CHOP in CCL-244 and SW480 cells. In addition, endoplasmic reticulum stress inhibitor 4-phenylbutyric acid or CHOP knockdown could prevent FAN-induced apoptosis. Thus, FAN induced apoptosis of human colorectal cancer through activation of endoplasmic reticulum stress.

Gelsolin Inhibits the Proliferation of Colon Cancer Cells by Enhancing the Expression of TNFR2/CASP10 as a Death Receptor Pathway.

Colon cancer has the second highest incidence rate of digestive system tumors. It relies on surgical treatment, radiotherapy and chemotherapy, and targeted drug therapy. To study the mechanism of GSN in the proliferation of colon cancer cells. The expression of gelsolin (GSN) was analyzed with the data of colon cancer patients in the TCGA database. SW620 cells were treated by GSN in vitro and the gene expression was detected by immunoblotting and quantitative PCR. The expression of GSN was found significantly low in colon cancer cells and correlated with the prognosis of patients. The SW620 cell line cultured in vitro was treated with exogenous GSN. SW620 can be significantly inhibited above the concentration of 250 μg/ml. The results of immunoblotting and quantitative PCR showed that exogenous GSN can effectively improve the transcription level of death receptor-related pathway genes such as TNFR2 and CASP10. This study found that GSN inhibited the proliferation of SW620 cells in vitro by upregulating the expression of death receptor pathway-related proteins.

Induction of Apoptosis and Decrease of Autophagy in Colon Cancer Cells by an Extract of Lyophilized Mango Pulp.

Previous studies have indicated that mango fruit has a chemopreventive capacity against colorectal cancer cells. The objective of this research was to evaluate the effect of an aqueous extract of lyophilized mango pulp (LMPE) on colon adenocarcinoma cells (SW480) and their metastatic derivatives (SW620) death and cellular invasion. DNA fragmentation was assessed by TUNEL assay; autophagy and expression of DR4 and Bcl-2 by flow cytometry; the expression of 35 apoptosis-related proteins and of matrix metalloproteinases 7 and 9 by immunodetection; and the invasive capacity of the cells by Boyden chamber. The results showed that LMPE at 30 mg/mL and 48 h of exposure results in DNA fragmentation and apoptosis in SW480 (p < 0.001) and SW620 (p < 0.01) cells. Additionally, LMPE decreased autophagy in the SW480 and SW620 cell lines (p < 0.001), which could sensitize them to the DNA damage generated by LMPE. The LMPE did not modulate the expression of matrix metalloproteinases 7 and 9, nor did it affect cellular invasion processes in the SW480 and SW620 cell lines. In conclusion, LMPE induces apoptosis and decreases autophagy in SW480 and SW620 cells.

MiR-210 Expression Is Strongly Hypoxia-Induced in Anaplastic Thyroid Cancer Cell Lines and Is Associated with Extracellular Vesicles and Argonaute-2.

Hypoxia, or low oxygen tension, is frequently found in highly proliferative solid tumors such as anaplastic thyroid carcinoma (ATC) and is believed to promote resistance to chemotherapy and radiation. Identifying hypoxic cells for targeted therapy may thus be an effective approach to treating aggressive cancers. Here, we explore the potential of the well-known hypoxia-responsive microRNA (miRNA) miR-210-3p as a cellular and extracellular biological marker of hypoxia. We compare miRNA expression across several ATC and papillary thyroid cancer (PTC) cell lines. In the ATC cell line SW1736, miR-210-3p expression levels indicate hypoxia during exposure to low oxygen conditions (2% O2). Furthermore, when released by SW1736 cells into the extracellular space, miR-210-3p is associated with RNA carriers such as extracellular vesicles (EVs) and Argonaute-2 (AGO2), making it a potential extracellular marker for hypoxia.

Five new limonoids isolated from Walsura robusta

Five new toosendanin limonoids with highly oxidative furan ring walsurobustones A-D (1–4), and one new furan ring degraded limonoid walsurobustone E (5) together with one known compound toonapubesic acid B (6) were isolated from the leaves of Walsura robusta. Their structures were elucidated by NMR and MS data. Especially, the absolute configuration of toonapubesic acid B (6) was confirmed by X-ray diffraction study. Compounds 1–6 exhibited good cytotoxicity against the cancer cell lines HL-60, SMMC-7721, A-549, MCF-7, and SW480.

Transcription factor B-MYB activates lncRNA CCAT1 and upregulates SOCS3 to promote chemoresistance in colorectal cancer

Currently, resistance to oxaliplatin (OXA) has become an important obstacle to improving the clinical outcome of patients with colorectal cancer (CRC). Moreover, long non-coding RNAs (lncRNAs) have been documented in cancer chemoresistance, and our bioinformatic analysis suggested an involvement of lncRNA CCAT1 in CRC development. In this context, this study aimed to clarify the upstream and downstream mechanisms underpinning the effect of CCAT1 in the resistance of CRC to OXA. The expression of CCAT1 and the upstream B-MYB in the CRC samples was predicted by bioinformatics analysis and then verified using RT-qPCR in CRC cell lines. Accordingly, overexpression of B-MYB and CCAT1 was observed in CRC cells. SW480 cell line was used for the construction of OXA-resistant cell line (SW480R). Ectopic expression and knockdown experiments of B-MYB and CCAT1 were conducted in SW480R cells to delineate their roles in the malignant phenotypes and half-maximal (50%) inhibitory concentration (IC50) of OXA. It was found that CCAT1 promoted the resistance of CRC cells to OXA. Mechanistically, B-MYB transcriptionally activated CCAT1, which recruited DNMT1 to inhibit SOCS3 expression through elevating the SOCS3 promoter methylation. By this mechanism, the resistance of CRC cells to OXA was enhanced. Meanwhile, these in vitro findings were reproduced in vivo on xenografts of SW480R cells in nude mice. To sum up, B-MYB might promote the chemoresistance of CRC cells to OXA via regulating the CCAT1/DNMT1/SOCS3 axis.

In vitro antioxidant, anti-inflammatory, and anticancer activities of mixture Thai medicinal plants

BackgroundThe phytochemical study of medicinal plants is rapidly gaining popularity with many pharmacologic effects. This study aims to determine the antioxidant capacity as well as anticancer and antimigration activities of Clear belongs Plus extract (CBL-P) which consisted of five medicinal plants namely, Alpinia galanga, Piper nigrum, Citrus aurantifolia, Tiliacora triandra, and Cannabis sativa on human colon cancer cells SW620 and HCT116 cell lines, and human non-small cell lung cancer cells A549 and NCI-H460 cell lines.MethodsIn this study the dried-plant powder was extracted using 90% ethanol. Additionally, CBL-P was studied antioxidative activity via DPPH and ABTS assays and anti-inflammatory activities using nitric oxide assay using Griess reaction. Antiproliferation and antimigration of CBL-P were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and scratch assay.ResultsThe results showed that CBL-P had potent antiproliferative activity with IC50 values in a concentration- and time-dependent manners for all four cell lines. CBL-P also possessed potent antimigration activity against all studied cancer cells. CBL-P demonstrated antimigration activity on four different types of cancer cells (A549, NCI-H460, HCT116, and SW620) after 48 h of incubation, with the greatest effect seen at the highest concentration tested (15 μg/mL) in A549 cells (10.23% of wound closure) and NCI-H460 cells (9.16% of wound closure). CBL-P was also effective in reducing migration in HCT116 and SW620 cells, with a range of closure area from 10—50%. In addition, CBL-P had antioxidant activity with IC50 values of 8.549 ± 0.241 mg/mL and 2.673 ± 0.437 mg/mL for DPPH and ABTS assays, respectively. CBL-P also showed anti-inflammatory activity with the best inhibitory activity on NO production at a concentration of 40 μg/mL.ConclusionIn conclusion, the mixture extract possessed antioxidant and anti-inflammatory activity. Furthermore, the mixture plant extract significantly exhibited antiproliferative and antimigration activities on SW620, HCT116, A549, and NCI-H460 cells (P ≤ 0.05). Taken together, our results suggest that medicinal plants may have synergistic effects that could potentially enhance the effectiveness of cancer treatment when used as adjuvants. These findings provide a solid scientific foundation for future efforts to explore the mechanism of action.

Dual-targeting therapy against HER3/MET in human colorectal cancers.

Colorectal cancer (CRC) is the most common malignancy in the world, and novel molecular targeted therapies for CRC have been vigorously pursued. We searched for novel combination therapies based on the expression patterns of membrane proteins in CRC cell lines. A positive correlation was observed between the expression of human pidermal growth factor receptor (HER) 3 and mesenchymal-to-epithelial transition factor (MET) on the cell surface of CRC cell lines. The brief stimulation of HER3/MET-high SW1116 CRC cells with both neuregulin-1 (NRG1) and hepatocyte growth factor enhanced ERK phosphorylation and cell proliferation more than each stimulation alone. In addition, a prolonged NRG1 stimulation resulted in the tyrosine phosphorylation of MET. In this context, the Forkhead Box protein M1 (FOXM1)-regulated tyrosine phosphorylation of MET by NRG1 was demonstrated, suggesting the existence of a signaling pathway mediated by FOXM1 upon the NRG1 stimulation. Since the co-expression of HER3 and MET was also demonstrated in in vivo CRC tissues by immunohistochemistry, we investigated whether the co-inhibition of HER3 and MET could be an effective therapy for CRC. We established HER3-and/or MET-KO SW1116 cell lines, and HER3/MET-double KO resulted in the inhibition of in vitro cell proliferation and in vivo tumor growth in nude mice by SW1116 cells. Furthermore, the combination of patritumab, an anti-HER3 fully human mAb, and PHA665752, a MET inhibitor, markedly inhibited in vitro cell proliferation, 3D-colony formation, and in vivo tumor growth in nude mice by SW1116 cells CONCLUSION: The dual targeting of HER3/MET has potential as CRC therapy.

Ethacridine Regulation of JAK/STAT/ERK Signaling Pathway in Colon Cancer Cells SW620: In vitro Approach

Background Ethacridine have anticancer effects by inhibiting regulatory transcription factors and cell viability in various cancer cells. To investigate the effect of ethacridine on colorectal cancer cell lines, SW620 was studied via regulation of JAK/STAT/ERK signaling pathway. Materials and Methods Different doses of ethacridine (5–35 µM) expressed antiproliferative effects by decreasing the viability in a dose-dependent manner and the IC50 value was found to be 10 µM. Results Subsequent treatment with 10 µM of ethacridine showed that it induced mitochondrial dysfunction and reactive oxygen species generation. DAPI and PI staining assays revealed prominent apoptotic cells under the microscope when treated with 10 µM of ethacridine. In the mRNA expression study performing RT-PCR of apoptotic markers, cyclin-D1, Bax, Bcl-2, caspase 3, C-Myc, and surviving, enhanced levels of these markers were suppressed, which was inversely proportional to the levels of apoptotic enhancers namely Bax and caspase-3. It was also observed that increased NF-κB, IL-6, TNF-α, and COX-2 in colorectal cancer are suppressed by ethacridine. The expressions of JAK/STAT/ERK were also significantly suppressed after ethacridine treatment in SW620 cell lines. Conclusion In summary, it was corroborated that ethacridine promoted apoptosis in colon cancer cells by inhibiting quite a few cell signaling factors.

One-Step Phytofabrication Method of Silver and Gold Nanoparticles Using Haloxylon salicornicum for Anticancer, Antimicrobial, and Antioxidant Activities.

Among various routes of metallic nanoparticle (NPs) fabrication, phytosynthesis has significant advantages over other conventional approaches. Plant-mediated synthesis of NPs is a fast, one-step, ecobenign, and inexpensive method with high scalability. Herein, silver (Ag) and gold (Au)-NPs were extracellularly synthesized using aqueous Haloxylon salicornicum (H@Ag-, H@Au-NPs) leaf extracts. GC-MS was performed to analyze the chemical compositions of H. salicornicum extract. H@Ag- and H@Au-NPs were characterized via UV-Vis spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission and scanning electron microscopy, and Zetasizer. H@Ag- and H@Au-NPs have surface plasmon resonance at 435.5 and 530.3 nm, respectively. FTIR and GC-MS data suggest that secondary plant metabolites and hydrocarbons might be responsible for the reduction and stabilization of NPs. XRD demonstrated that both NPs have a crystalline nature. H@Ag-NPs have a uniform spherical shape, whereas H@Au-NPs are spherical with few oval and triangular shapes, and their average nanosizes were 19.1 ± 0.8 and 8.1 ± 0.3 nm, respectively. Hydrodynamic diameters of H@Ag-NPs and H@Au-NPs were 184.7 nm, 56.4, and 295.4 nm, and their potential charges were -24.0 and -24.4 mV, respectively. The inhibitory activity of 500 µg/mL H@Ag- and H@Au-NPs was tested against Sw480, Sw620, HCT-116, and Caco-2 colon cancer cell lines and two normal cell lines, including HFs and Vero. H@Ag-NPs revealed potent anticancer activity against all cancer cells at low concentrations. Sw480 was the most sensitive cell to H@Ag-NPs, whereas Sw620 was the least permeable one. These findings suggested that the antiproliferative activity of H@Ag-NPs is cell-response-dependent and may be influenced by a variety of factors, including the cellular metabolic state, which influences cellular charge and interactions with charged NPs. Although H@Au-NPs were smaller, their reactivity against cancer cells was weak, suggesting that the chemical properties, metal structure, quantity and chemistry of the functional groups on the NP surface may influence their reactivity. The biocidal activity of 1 mg/mL H@Ag- and H@Au-NPs against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Klebsiella pneumoniae was assessed. H@Ag-NPs showed biocidal activity against Gram-positive bacteria compared to Gram-negative bacteria, whereas H@Au-NPs showed no inhibitory activity. FRAP and DPPH assays were used to determine the scavenging activity of the plant extracts and both NPs. H@Ag-NPs (1 mg/mL) had the greatest scavenging activity compared to tested drugs. These findings suggest that H@Ag-NPs are potent anticancer, antibacterial, and antioxidant agents, while H@Au-NPs may be used as a drug vehicle for pharmaceutical applications.

Bioactive sorbicillinoids from a rhizospheric soil-derived Paecilomyces sp. KMU21009

A new hybrid sorbicillinoid named paeciureallin (1) and a new monomeric sorbicillinoid named paecillyketide (2), along with six known analogues (3–8), were isolated from the rhizospheric soil-derived fungus Paecilomyces sp. KMU21009 associated with Delphinium yunnanense. Their structures were elucidated by extensive spectroscopic analysis and comparison with literature values. Paeciureallin (1) is the first example of hybrid sorbicillinoids possessing a rare sorbicillinoid urea unit and containing a β-D-ribofuranose functionality. In pharmacological studies, compounds 1 and 2 were evaluated for in vitro anti-inflammatory and cytotoxic activities. Paeciureallin (1) exhibited moderate cytotoxicity against SW480 and A549 cell lines, and the IC50 values were 32.0 ± 0.1 and 34.4 ± 2.0 μM, respectively.

Aspirin increases the efficacy of gemcitabine in pancreatic cancer by modulating the PI3K/AKT/mTOR signaling pathway and reversing epithelial‑mesenchymal transition.

Gemcitabine is regarded as a standard medication for patients with pancreatic cancer. The aim of the present study was to investigate the impact of aspirin (ASA) on the efficacy of gemcitabine in pancreatic cancer and the potential mechanism. The SW1990 and BxPC-3 human pancreatic cell lines were treated with 2 mmol/l ASA and/or 1 mg/l gemcitabine. The effects of the treatments were tested on the viability, migration and invasion of the cells using MTT, wound healing and Transwell invasion assays. In addition, cell apoptosis was evaluated via flow cytometry with Annexin V-FITC/PI and the western blotting of Bax and Bcl-2. The expression of epithelial-mesenchymal transition (EMT)-associated proteins and activation of the PI3K/AKT/mTOR pathway were also assessed using western blotting. The results reveal that ASA increased the efficacy of gemcitabine in reducing the proliferation, migration and invasion of pancreatic cancer cells and increasing their apoptosis. These effects are associated with inhibition of the PI3K/AKT/mTOR pathway and the reversal of EMT. Thus, the combined use of ASA and gemcitabine is suggested to be a potential therapeutic strategy for patients with pancreatic cancer.

Generation of TGFβR2(-1) neoantigen-specific HLA-DR4-restricted T cell receptors for cancer therapy

BackgroundAdoptive transfer of patient’s T cells, engineered to express a T cell receptor (TCR) with defined novel antigen specificity, is a convenient form of cancer therapy. In most cases, major...

LncRNA TINCR knockdown inhibits colon cancer cells via regulation of autophagy.

The present study aimed to evaluate the effects of long noncoding (lnc)RNA TINCR ubiquitin domain containing (TINCR) on the development of colon cancer, and the specific underlying mechanisms. The present study used adjacent healthy and cancer tissues obtained from patients with colon cancer and measured lncRNA TINCR expression using reverse transcription-quantitative (RT-q) PCR and in situ hybridization assays. Moreover, associations between lncRNA TINCR and clinicopathology and prognosis were also investigated. In addition, the gene and protein expression levels of lncRNA TINCR, mTOR, LC 3B, P62, and Beclin1 were measured using RT-qPCR and western blotting assays. Cell proliferation, apoptosis, invasion, and migration were measured using MTT, Edu staining, flow cytometry, TUNEL, Transwell, and wound-healing assays, and cell ultrastructure and LC 3B activation were measured using transmission electron microscopy and cellular immunofluorescence. Results of the present study demonstrated that lncRNA TINCR expression was significantly upregulated in colon cancer tissues, and the overall survival of the low-expression group was significantly increased, compared with that of the high-expression groups. In addition, the results of the present study demonstrated that lncRNA TINCR was associated with clinicopathology in patients with colon cancer. Moreover, following lncRNA TINCR knockdown using transfection with small interfering RNA-TINCR, results of the present study demonstrated that cell proliferation was significantly reduced, while cell apoptosis was significantly increased. In addition, cell invasion and migration were significantly reduced, and autophagy was increased in HT-29 and SW620 cell lines. However, following treatment with an mTOR agonist (an autophagy inhibitor), biological activities were significantly increased in HT-29 and SW-620 cell lines. Collectively, these results demonstrated that lncRNA TINCR may induce colon cancer development through the regulation of autophagy.

Therapeutic effects of kefir peptides on adjuvant-induced arthritis in rats through anti-inflammation and downregulation of matrix metalloproteinases

AimsRheumatoid arthritis (RA) is a chronic autoimmune disease. Its pathological features are synovial inflammation, bone erosion, and joint structural damages. Our previous studies have shown that kefir peptides (KPs) can reduce cardiovascular disease, osteoporosis and renal inflammation. In this study, we further evaluate the efficacy of KPs on adjuvant-induced arthritis (AIA) in a rat model. Main methodsAfter the 14th day of adjuvant induction, rats were subsequently orally administered KPs (83 or 166 mg/day/kg) or tofacitinib (6.2 mg/day/kg) for 14 days. On the 28th day, the rats were anesthetized with isoflurane for ultrasonic, in vivo imaging system (IVIS), and radiographic imaging and then sacrificed for ankle tissues collection and analysis. In vitro, IL-1β-treated human synovial cells (SW982) were subjected to anti-arthritis mechanism study in the presence of KPs. Key findingsThe results of ultrasonography, radiograph, histology, the expression of matrix metalloproteinases (MMPs), inflammatory cytokines and RANKL/OPG ratio demonstrated decreasing severity of synovitis and bone erosion in the ankle joints after KPs treatment. Activation of the NF-κB and MAPK pathways was significantly reduced in KPs treated AIA group. Furthermore, KPs attenuated IL-1β-induced inflammatory cytokine production and the expression of MMPs in a human synovial cell line SW982. These results demonstrated that KPs alleviated adjuvant-induced arthritis in rats by inhibiting IL-1β-related inflammation and MMPs production. SignificanceWe concluded that KPs can exhibit anti-inflammatory effects by reducing the levels of macrophage-related inflammatory cytokines and MMPs, thus alleviating bone erosion in the ankle joint and constituting a potential therapeutic strategy for rheumatoid arthritis.