Inhibits Colon Cancer Cell Research Articles

Estrogen Receptor Beta (ERβ) Mediated-CyclinD1 Degradation via Autophagy Plays an Anti-Proliferation Role in Colon Cells.

Dysfunction of autophagic degradation machinery causes tumorigenesis, including colorectal cancer (CRC). Overexpression of CyclinD1 in CRC has been reported. Recent evidence also suggests that ERβ deficiency is related to the pathogenesis of CRC. Very little is known, however, about the detailed molecular mechanisms underlying the relationship among ERβ, autophagy, and CyclinD1 in CRC. Here, results showed that ERβ played an anti-proliferation role in HCT116 through impairing cell cycle but not apoptosis. Additionally, CyclinD1 accumulation was increased in response to chloroquine (CQ) or in MEF Atg7 knockout cells. Further, ERβ could inhibit the mammalian target of rapamycin (mTOR) or activate Bcl-2/adenovirus E1B 19-kDa-interacting protein 3 (BNIP3) to promote autophagy in HCT116. In summary, these results indicate that ERβ-mediated CyclinD1 degradation can inhibit colon cancer cell growth via autophagy.

VSTM2A suppresses colorectal cancer and antagonizes Wnt signaling receptor LRP6.

Hyperactivation of Wnt/β-catenin signaling pathway is a critical step in colorectal tumorigenesis. In this study, we identified that V-set and transmembrane domain containing 2A (VSTM2A) was a top-downregulated secreted protein that negatively regulated Wnt singling pathways in colorectal cancer (CRC). We investigated the functional mechanisms and clinical implication of VSTM2A in CRC.Methods: Function of VSTM2A was investigated in vitro and in vivo. VSTM2A binding partner was identified by mass spectrometry, immunoprecipitation and Western blot. The clinical impact of VSTM2A was assessed in 355 CRC patients and TCGA cohort.Results: VSTM2A protein was prominently silenced in CRC tumor tissues and cell lines mediated by its promoter hypermethylation. VSTM2A DNA promoter hypermethylation and VSTM2A protein downregulation was associated with poor survival of CRC patients. Ectopic expression of VSTM2A inhibited colon cancer cell lines and organoid growth, induced CRC cells apoptosis, inhibited cell migration and invasion, and suppressed growth of xenograft tumors in nude mice. VSTM2A was released from CRC cells through a canonical secretion pathway. Secreted VSTM2A significantly suppressed Wnt signaling pathway in colon cancer cells. Wnt signaling co-receptor LDL receptor related protein 6 (LRP6) was identified as a cell membrane binding partner of VSTM2A. Using deletion/mutation and immunoprecipitation, we demonstrated that VSTM2A bound to LRP6 E1-4 domain with its IgV domain. VSTM2A suppressed LRP6 phosphorylation in a time and dose dependent manner, and induced LRP6 endocytosis and lysosome-mediated degradation, which collectively contributing to the inactivation of Wnt signaling.Conclusions: VSTM2A is a novel antagonist of canonical Wnt signaling by directly binding to LRP6 and induces LRP6 endocytosis and degradation. VSTM2A is a potential prognostic biomarker for the outcome of CRC patients.

The Bioactive Ingredients in Niuli Lactucis Agrestibus Possess Anticancer Effects

In the field of medicine, natural treatments are becoming increasingly vital towards the cure of cancer. We investigated the effect of various concentrations of Niuli​ Lactucis Agrestibus​ crude extract on the survival percentage and proliferation rate of COLO320DM adenocarcinoma cells. Our experimental process consisted of the following methods: a Trypan Blue Cell exclusion assay for viability, a cancer cell migration assay, and a protein expression test. These tests were performed using varying concentrations of crude extract to test the impact of the chemicals in the extract on colorectal cancer cells. Our results for the cell viability test showed that the crude extract significantly increased the death rate of colon cancer cells, but not of healthy cells. Furthermore, the results suggested that increasing the concentration of crude extract inhibited colon cancer cell migration. In addition, we observed that the Niuli extract significantly upregulated the expression of p21 and p27, two key proteins in the cell cycle. These results indicate that the presence of bioactive ingredients in Niuli lettuce can exhibit anti-colon cancer properties. Further experimentation will be carried out to purify and identify the chemicals found within the crude extract that contain the potential for the treatment of colorectal cancer.

Cell growth inhibition by 3-deoxysappanchalcone is mediated by directly targeting the TOPK signaling pathway in colon cancer

BackgroundColorectal cancer is one of the most common causes of cancer death worldwide. Unfortunately, chemotherapies are limited due to many complications and development of resistance and recurrence. The T-lymphokine-activated killer cell-originated protein kinase (TOPK) is highly expressed and activated in colon cancer, and plays an important role in inflammation, proliferation, and survival of cancer cells. Therefore, suppressing TOPK activity and its downstream signaling cascades is considered to be a rational therapeutic/preventive strategy against colon cancers. Purpose3-Deoxysappanchalcone (3-DSC), a component of Caesalpinia sappan L., is a natural oriental medicine. In this study, we investigated the effects of 3-DSC on colon cancer cell growth and elucidated its underlying molecular mechanism of targeting TOPK. Study design and methodsTo evaluate the effects of 3-DSC against colon cancer, we performed cell proliferation assays, propidium iodide- and annexin V-staining analyses and Western blotting. Targeting TOPK by 3-DSC was identified by a kinase-binding assay and computational docking models. Results3-DSC inhibited the kinase activity of TOPK, but not mitogen-activated protein kinase (MEK). The direct binding of 3-DSC with TOPK was explored using a computational docking model and binding assay in vitro and ex vivo. 3-DSC inhibited colon cancer cell proliferation and anchorage-independent cell growth, and induced G2/M cell cycle arrest and apoptosis. Treatment of colon cancer cells with 3-DSC induced expression of protein that are involved in cell cycle (cyclin B1) and apoptosis (cleaved-PARP, cleaved-caspase-3, and cleaved-caspase-7), and suppressed protein expressions of extracellular signal-regulated kinase (ERK)-1/2, ribosomal S6 kinase (RSK), and c-Jun, which are regulated by the upstream kinase, TOPK. Conclusion3-DSC suppresses colon cancer cell growth by directly targeting the TOPK- mediated signaling pathway.

Long noncoding RNA PCAT6 inhibits colon cancer cell apoptosis by regulating anti-apoptotic protein ARC expression via EZH2

ABSTRACTProstate cancer-associated ncRNA transcript 6 (PCAT6) is a long intergenic noncoding RNA that is involved in the progression of prostate and lung cancer, acting as a potential diagnostic and prognostic biomarker in nonsmall cell lung cancer. However, little is known about PCAT6 expression and its clinical significance in colon cancer. Here, we aimed to investigate the clinical significance of PCAT6 in colon cancer and its underlying mechanism. The expression of PCAT6 was analyzed in colon cancer tissues using public databases, and a series of in vitro and in vivo experiments was performed to investigate the biological functions of PCAT6 in colon cancer cells and the underlying mechanisms. Our results demonstrated that PCAT6 was upregulated in colon cancer tissues compared with that in noncancerous tissues, correlating with poorer clinical stages and a worse survival status. In vitro and in vivo experiments illustrated PCAT6 promoted cell growth and inhibited cell apoptosis in colon cancer. Mechanistically, PCAT6 enhanced the coenrichment of EZH2 and H3K4me3 at the apoptosis repressor with caspase recruitment domain (ARC) genomic region, promoting the transcriptional activity of ARC. Our data highlighted that PCAT6 acts as a key activator of ARC expression by forming a complex with EZH2, inhibiting cell apoptosis and contributing to colon cancer progression. These findings elucidated that PCAT6 may be a novel prognostic predictor and therapeutic target of colon cancer.

Chelate-soluble pectin fraction from papaya pulp interacts with galectin-3 and inhibits colon cancer cell proliferation

Colorectal cancer has an overexpression of galectin-3 that is related to cancer progression. A decreased risk of colon cancer can be related to consumption of dietary fibers, but the entire mechanism by which this protection occurs remains unclear. Pectin is a type of dietary fiber that possesses β-galactosides and can bind and inhibit galectin-3–mediated effects. Papaya fruit has a massive cell wall disassembling during ripening that naturally changes its pectin structure. Our work shows that different points in the ripening time of papaya fruit exhibit pectins (chelate-soluble fractions; CSF) that can or cannot inhibit galectin-3. The fraction that inhibits galectin-3 (3CSF) also diminishes the proliferation of colon cancer cell lines, and it is derived from an intermediate point of papaya ripening. Therefore, we related this to a papaya pectin structure-dependent effect, and the papaya fruit seems to have a pectin structure that is promising in decreasing the risk of colon cancer development.

Esculentoside H inhibits colon cancer cell migration and growth through suppression of MMP-9 gene expression via NF-kB signaling pathway.

A water-soluble saponin, Esculentoside H (EsH), 3-O-(O-β-d-glucopyranosyl-(1→4)-β-d-xylopyranosyl)-28-β-d-glucopyranosylphytolaccagenin has been isolated and purified from the root extract of perennial plant Phytolacca esculenta. EsH is known to be an anticancer compound, having a capacity for TNF-α release. However, the effects of EsH on migration and growth in tumor cells have not yet been reported. In the current study, the suppressive effects of EsH on phorbol 12-myristate 13-acetate (PMA)-induced cell migration were examined in murine colon cancer CT26 cells and human colon cancer HCT116 cells. Interestingly, the transwell assay and wound healing show that EsH suppresses the PMA-induced migration and growth potential of HCT116 and CT26 colon cancer cells, respectively. EsH dose-dependently suppressed matrix metalloproteinases-9 (MMP-9) expression that was upregulated upon PMA treatment in messenger RNA levels and protein secretion. Since the expression of MMP-9 is correlated with nuclear factor-κB (NF-κB) signaling, it has been examined whether EsH inhibits PMA-induced IκB phosphorylation that leads to the suppression of NK-κB nuclear translocation. EsH repressed the phosphorylation level of JNK, but not extracellular signal-regulated kinase and p38 signaling when the cells were treated with PMA. Overall, these results demonstrated that EsH could suppress cancer migration through blockage of the JNK1/2 and NF-κB signaling-mediated MMP-9 expression.

Cordycepin induces Bax‑dependent apoptosis in colorectal cancer cells.

Cordycepin, or 3′-deoxyadenosine, is a derivative of the nucleoside adenosine. Initially extracted from the fungus Cordyceps militaris, cordycepin exhibits antitumor activity against certain cancer cell lines; however, the mechanism by which cordycepin counteracts colorectal cancer (CRC) remains poorly understood. The aim of the present study was to explore the underlying mechanisms of cordycepin against human CRC. To investigate the molecular mechanisms of cordycepin against colon cancer and in driving apoptosis, p53 and Bcl-2-like protein 4-null (Bax−/−) colon cancer HCT116 cell lines were used. Cell viability and growth were repressed in a dose-dependent manner in cells treated with cordycepin. Treatment with cordycepin resulted in increased apoptosis in HCT116 cells; however, flow cytometic analysis demonstrated that apoptosis was notably decreased in the Bax−/− HCT116 cell lines, but not in the p53−/− HCT116 cell lines. Furthermore, cordycepin exposure resulted in the translocation of Bax from the cytosol to the mitochondria and the subsequent release of cytochrome c from the mitochondria. Results from the present study demonstrated that cordycepin inhibited colon cancer cell growth in vitro and this appears to be through the endogenous Bax-dependent mitochondrial apoptosis pathway, which suggested a molecular mechanism for cordycepin against human colon cancer. These results indicated the possibility of cordycepin as a novel drug for the prevention of colon cancer.

Dihomo-\u03b3-linolenic acid inhibits xenograft tumor growth in mice bearing shRNA-transfected HCA-7 cells targeting delta-5-desaturase

BackgroundWe previously demonstrated that knockdown of delta-5-desaturase via siRNA transfection together with dihomo-γ-linolenic acid supplementation inhibited colon cancer cell growth and migration, by promoting the production of the anti-cancer byproduct 8-hydroxyoctanoic acid from Cyclooxygenase-2-catalyzed dihomo-γ-linolenic acid peroxidation. Here, we extend our study to investigate the effects of delta-5-desaturase-knockdown and the resulting intensified dihomo-γ-linolenic acid peroxidation in xenograft tumor mice model.MethodsFour-week old nude mice bearing the human colon cancer cell HCA-7/C29 vs. its delta-5-desaturase knockdown analog (via shRNA transfection) were subject to 4-week treatments of: vehicle control, dihomo-γ-linolenic acid supplementation, 5-Fluorouracil, and combination of dihomo-γ-linolenic acid and 5-Fluorouracil. Tumor growth was monitored during the treatment. At the endpoint, the mice were euthanized and the tumor tissues were collected for further mechanism analysis.ResultsDelta-5-desaturase knockdown (shRNA) together with dihomo-γ-linolenic acid supplementation increased 8-hydroxyoctanoic acid production to a threshold level in xenograft tumors, which consequently induced p53-dependent apoptosis and reduced tumors significantly. The promoted 8-hydroxyoctanoic acid formation was also found to suppress the tumors’ metastatic potential via regulating MMP-2 and E-cadherin expressions. In addition, our in vivo data showed that delta-5-desaturase knockdown along with dihomo-γ-linolenic acid supplementation resulted in anti-tumor effects comparable to those of 5-Fluorouracil.ConclusionsWe have demonstrated that our paradigm-shifting strategy of knocking down delta-5-desaturase and taking advantage of overexpressed Cyclooxygenase-2 in tumor cells can be used for colon cancer suppression. Our research outcome will lead us to develop a better and safer anti-cancer therapy for patients.

RACK1 promotes tumorigenicity of colon cancer by inducing cell autophagy

RACK1 is upregulated in the various types of human cancers, and considered to play a role in the development and progression of human cancer. However, the role and mechanism of RACK in the colon cancer are poorly understood. In this study, we detected RACK1 expression in 63 normal colonic mucosa, 60 colonic inflammatory polyps, 60 colonic adenomas, 180 colon adenocarcinomas, and 40 lymph node metastases by immunohistochemistry, and observed that RACK1 expression was progressively elevated in the carcinogenic process of human colonic epithelium, and RACK1 expressional levels were positively correlated with the malignant degree and lymph node metastasis of colon cancers, and negatively correlated with the patient survival. With a combination of loss-of-function and gain-of-function approaches, we observed that RACK1 promoted colon cancer cell proliferation, inhibited colon cancer cell apoptosis, and enhanced the anchorage-independent and xenograft growth of colon cancer cells. Moreover, we found that RACK1-induced autophagy of colon cancer cells; RACK1-induced autophagy promoted colon cancer cell proliferation and inhibited colon cancer cell apoptosis. Our data suggest that RACK1 acts as an oncogene in colon cancer, and RACK1-induced autophagy promotes proliferation and survival of colon cancer, highlighting the therapeutic potential of autophagy inhibitor in the colon cancer with high RACK1 expression.

Both Bupivacaine and Levobupivacaine inhibit colon cancer cell growth but not melanoma cells in vitro

BackgroundRetrospective studies indicate that the use of regional anaesthesia causes a reduction in cancer recurrence after oncological surgery, which could be due to anaesthetic’s negating effect on immunosuppression related to the surgical stress response. Local anaesthetics may also exert direct suppressive effects on malignant cells, an area where further investigation is urgently needed.MethodsHuman colon cancer cells and human melanoma cells were cultured and then treated with 1 mM bupivacaine or levobupivacaine for up to 24 or 48 h. Their migratory ability was measured by scratch assay, proliferation determined with Ki67 immunofluorescence staining, and apoptosis accessed with annexin V and PI staining on flow cytometry. The effects of bupivacaine and levobupivacaine on cellular signaling and molecular response, specifically, on endoplasmic reticulum stress (ERS), were studied with immunostaining and western blot.ResultsIn colon cancer cells, treatment with bupivacaine and levobupivacaine significantly inhibited cell migration (**p < 0.01, ***p < 0.001; n = 4) and proliferation (**p < 0.01; n = 4), while increasing the expression of CHOP (***p < 0.001; n = 4) and decreased the expression of Grp78 (*p < 0.05; n = 4). These effects were not mirrored by melanoma cells, such that no significant increase in apoptosis was seen in either melanoma cell lines following treatment.ConclusionThese in vitro data suggested that both bupivacaine and levobupivacaine suppress colorectal adenocarcinoma cell proliferation and migration, which are concurrent with increased endoplasmic reticulum stress. Conversely, melanoma cells are more resilient to these two commonly used local anaesthetics. Further in vivo studies or clinical trials are needed.

Graphene Oxide Immobilized PLGA-polydopamine Nanofibrous Scaffolds for Growth Inhibition of Colon Cancer Cells.

Graphene oxide (GO)/poly (lactide-co-glycolic acid) (PLGA) scaffolds have promising applications in the biomedical field. However, greater attention is focused on the incorporated system and its applications in normal cells. In this work, a novel GO immobilized PLGA nanofibrous scaffold assisted by polydopamine (PLGA-PDA-GO) is developed for growth inhibition of HT-29 colon cancer cells. The interactions between GO and PDA are attributed to a π-π conjugate interaction and electrostatic attraction. In addition to the enhancement of thermal stability and mechanical strength, the surface roughness, hydrophilicity, and electro-activity of the scaffolds are significantly improved by immobilization of GO. The scaffolds show good inhibition of HT-29, and immobilized GO is observed to be in contact with but not internalized in HT-29 cells. The cytotoxicity mechanism of scaffolds toward HT-29 is attributed to intracellular activated reactive oxygen species that result from the physical interaction of the sharp GO edges and electrical signals of π-π stacking between PDA and GO.

HmiR-34c-3p upregulation inhibits the proliferation of colon cancer cells by targeting EIF3D.

Our study desired to investigate how miR-34c-3p regulates colon cancer cell proliferation and what is the relationship between miR-34c-3p and EIF3D. HCEpiC (normal human colonic epithelial cells), SW620, HT-29, SW480, and HCT-116 (human colon cancer cells lines) were used in our study. SW620 cells were chosen and divided into blank, miR-34c-3p mimics, miR-34c-3p NC, miR-34c-3p inhibitors, Lv-EIF3D, Lv-NC, and miR-34c-3p mimics+Lv-EIF3D groups. qRT-PCR was used for the detection of miR-34c-3p and EIF3D mRNA expressions. Dual-luciferase reporter assay was performed to investigate the effect of miR-34c-3p on EIF3D. Western blot was performed to detect EIF3D, cyclin D1, and c-Myc expressions. Clone formation and MTT assay were used to measure cell proliferation ability. colon cancer cells had lower miR-34c-3p expression, but higher EIF3D expression compared with HCEpiC. EIF3D mRNA expression was regulated negatively by miR-34c-3p. In the miR-34c-3p mimics group, colon cancer cell proliferation was significantly decreased, whereas c-Myc and cyclin D1 expressions were downregulated. Colon cancer cell proliferation in miR-34c-3p inhibitors and Lv-EIF3D groups was enhanced, and c-Myc and cyclin D1 expressions were decreased. The results suggested that by targeting EIF3D, miR-34c-3p inhibited colon cancer cell proliferation.

MiRNA expression profiles in Smad4-positive and Smad4-negative SW620 human colon cancer cells detected by next-generation small RNA sequencing.

Background and aimsSMAD4, as a tumor suppressive gene in human colon cancer, inhibits the metastasis of colon adenocarcinoma cells. However, the molecular mechanisms are unclear. miRNAs play an important role in the pathogenesis and progression of cancer.MethodsIn this study, a deep sequencing technique was used to screen Smad4-regulated miR-NAs in human colon cancer SW620 cell line. Using a next-generation small RNA sequencing approach, we compared the miRNA expression profiles of SW620 colon cancer cells transfected with smad4 lentiviral vector with those transfected with control vector. Six samples were selected and sequenced randomly each from control group (smad4-negative cell) and Smad4 group (Smad4-positive cells). Quantitative reverse transcription-PCR (qRT-PCR) and Western blot (WB) was used to validate the results of sequencing.ResultsSmad4 reexpression significantly upregulated 43 known miRNAs and downregulated 10 known miRNAs expression. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of predicted miRNAs targets showed that these genes were mainly involved in protein-binding transcription factor activity, vascular smooth muscle contraction, pathways in cancer metastasis, and phosphatidylinositol 3-kinase–Akt signal pathway. qRT-PCR and WB validated the partial results of sequencing. Reexpression of Smad4 inhibited colon cancer cell migration and invasion. Smad4 reexpression increased the expression of E-cadherin (E-cad) and decreased the Vimentin (Vim) and Matrix Metalloproteinase-9 expression. Restoration of SMAD4 results in a marked decrease of Vim by inhibiting p-AKT and p-EPHA2, but significantly increased the E-cad by AKT–EPHA2 pathways.ConclusionSmad4 inhibits the migration and invasion ability of colon cancer cells in vitro and this is the first report of Smad4-mediated miRNA expression profiling in Smad4-positive and Smad4-negative SW620 human colon cancer cells, which may help us better understand the role of Smad4 in inhibiting the metastasis of colon cancer cells and its possible molecular mechanisms.

Su Yang Decoction induces human colon carcinoma cell apoptosis by activating caspases.

Su Yang Decoction (SYD) is a popular healthcare product comprised of various brassicaceous vegetables known to exhibit anticancer activity. However, the effects of SYD on tumor growth, following its combination with brassicaceous vegetables into a compound formula, require further investigation. In the present study, a quality control of SYD was subjected to high-performance liquid chromatography for the quantitative and qualitative determination of sulforaphane, the main anticancer component of SYD. SYD inhibited colon cancer cell proliferation in a dose- and time-dependent manner and induced G1 phase arrest in colon cancer HT-29 cell lines. In addition, SYD triggered caspase-mediated apoptosis in a dose-dependent manner and induced the cleavage of poly (ADP-ribose) polymerase, tumor necrosis factor superfamily member 10, X-linked inhibitor of apoptosis, and truncated BH3 interacting domain death agonist. Furthermore, the expression of FADD-like interleukin-1β-converting enzyme (FLICE)-like inhibitory proteins (FLIPs) and long isoform of FLICE-inhibitory protein was reduced by SYD and the direct targeting of cellular-FLIP with small interfering RNA inhibited colon cancer cell proliferation and decreased the SYD concentration required for proliferation inhibition. SYD treatment was also associated with the translocation of proapoptotic BCL2 associated X, apoptosis regulator to the mitochondria and the release of cytochrome c from the mitochondria to the cytosol. The aforementioned results indicate that SYD exerts anti-colorectal cancer effects through an underlying mechanism that may involve caspase activation.

MicroRNA 429 regulates the expression of CHMP5 in the inflammatory colitis and colorectal cancer cells.

MicroRNAs (miRNAs) play an important role in the pathogenesis of human diseases by regulating the expression of target genes in specific cells or tissues. In this study, we analyzed the association between the MIR429 and its target gene, charged multivesicular body protein 5 (CHMP5), in human colon cancer cells and in a DSS-induced colitis mouse model. A luciferase reporter system was used to confirm the effect of MIR429 on CHMP5 expression. Protein or mRNA expression of the target gene and associated molecules were measured by Western blot or quantitative RT-PCR (qRT-PCR), respectively. Flow cytometry was used to compare cell viability or cell cycle progression. CHMP5 mRNA and protein expression was directly down-regulated by MIR429. We found that MIR429 inhibited colon cancer cell growth and cell cycle progression, and CHMP5 was overexpressed in the DSS-induced colitis mouse model and human ulcerative colitis (UC) tissues. Our findings show that CHMP5 is a direct target of MIR429 in human colon cancer cell lines and suggest that CHMP5 up-regulation as a result of reduced MIR429 expression in DSS-induced mice colitis tissues and human UC tissues may restrict apoptosis and promote cell proliferation.

Upregulation of HRD1 promotes cell migration and invasion in colon cancer

3-Hydroxy-3-methylglutaryl reductase degradation (HRD1) is an E3 ubiquitin ligase that functions by promoting degradation of misfolded proteins in processes such as embryogenesis and rheumatoid arthritis. However, little is known about the role of HRD1 in cancer. The aim of the present study was to investigate the expression pattern and functions of HRD1 in human colon cancer (CC). We found that HRD1 expression was increased significantly in human CC tissues, and its overexpression was associated with TNM stage, tumor differentiation, tumor invasive depth, and distant metastasis. Knockdown of HRD1 using small hairpin (sh) RNA plasmid significantly inhibited CC cell migration and invasion. Furthermore, the silencing of HRD1 decreased the expression of MMP-2 and MMP-9, which is critical for CC cell migration and invasion. Taken together, these results revealed that HRD1 is overexpressed in CC and promotes migration and invasion of CC cells. Inhibition of HRD1 may be considered as an effective anti-CC strategy.

PTBP1 promotes tumorigenesis by regulating apoptosis and cell cycle in colon cancer

Increased expression of polypyrimidine tract-binding protein 1 (PTBP1) has been observed in human ovarian tumors, glioblastomas, and breast cancer, but its biological roles in tumorigenesis is not fully clear. In the present research, we investigated the biological role of PTBP1 in colon cancer. We found that PTBP1 was overexpressed both in colon cancer cell lines and tissues. Tissue microarray analysis (TMA) indicated that low PTBP1 expression predicted a favorable overall survival for colon cancer patients. Using small interfering RNA technology, we found that down-regulation of PTBP1 significantly inhibited colon cancer cell growth/proliferation, and induced cell cycle arrest as well as apoptosis in vitro. Western blot analysis showed that siRNA PTBP1 could up-regulate the expression of cytoC, p53 and Bax as well as down-regulated p85, p-AKT, cyclinD1, CDK4 and Bcl2 compared to the control. Furthermore, Caspase-3 and PARP1 were activated when PTBP1 is knockdown. This study implies that PTBP1 plays an important role in tumorigenesis of colon cancer.

Overexpression of miRNA-143 Inhibits Colon Cancer Cell Proliferation by Inhibiting Glucose Uptake

MiRNA-143 overexpression is related to upregulated blood glucose level in diabetic mice, and downregulated miRNA-143 has been observed in several types of cancers, indicating its role as a tumor suppression miRNA. Glucose metabolism plays pivotal roles in tumor growth. Therefore, miRNA-143 may target glucose metabolism to inhibit tumor growth. Up to now, the functionality of miRNA-143 in colon cancer is still largely unknown. Our study was carried out to investigate the role of miRNA-143 in colon cancer and to explore the interactions between miRNA-143 and glucose uptake pathway. In this study we observed that miRNA-143 was downregulated in both colon biopsies (tumor tissues for colon cancer patients) and whole blood of colon patients than in healthy controls. Downregulation of miRNA-143 effectively distinguished colon cancer patients from healthy controls. Expression levels of miRNA-143 were found to be significantly correlated with tumor size but not distant tumor metastasis. MiRNA-143 overexpression inhibited glucose uptake and glucose transporter 1 (GLUT1) expression in colon cancer cells. MiRNA-143 overexpression also inhibited colon cancer cell proliferation. We therefore concluded that overexpression of miRNA-143 inhibited colon cancer cell proliferation by inhibiting glucose uptake.

Release of multifunctional peptides from kiwicha (Amaranthus caudatus) protein under in vitro gastrointestinal digestion.

The multifactorial origin of many chronic diseases provides a new framework for the development of multifunctional foods. In this study, the effect of in vitro simulated gastrointestinal digestion of kiwicha (Amaranthus caudatus) proteins on the release of multifunctional peptides was evaluated. Gastric digest showed higher angiotensin I converting enzyme (ACE) inhibitory activity while 60 min gastroduodenal digest showed the highest antioxidant, dipeptidyl peptidase IV (DPP-IV), α-amylase and Caco-2 cell viability inhibitory activities. Peptides >5 kDa were more effective in inhibiting colon cancer cell viability, whereas peptides <5 kDa were mainly responsible for the antioxidant, ACE, DPP-IV and α-amylase inhibitory activities. Thirteen peptides from amaranth sequenced proteins were identified. Structure-activity relationship analysis of the identified sequences pointed to three amaranth fragments, namely FLISCLL, SVFDEELS and DFIILE, as potential peptides able to concurrently exert antioxidant capacity and ability to inhibit both ACE and α-amylase. Five of thirteen peptides identified in kiwicha protein digests show high potential to exert multifunctional properties. Thus kiwicha proteins might start to gain importance as ingredients for functional foods for the prevention and/or management of chronic diseases related to oxidative stress, hypertension and/or diabetes. © 2018 Society of Chemical Industry.