Apoptosis In Colon Cancer Cells Research Articles

Aqueous extract of andean berry induces apoptosis in human colon cancer cells without mitochondrial damage

BACKGROUND: Andean berry contains several classes of phenolic compounds which have showed antioxidant and cytotoxic activity. OBJECTIVE: To characterize the Andean berry aqueous extract and to study their anti-proliferative mechanisms on SW480 and SW620 cell lines (human colon adenocarcinoma). METHODS: Total phenolic and total anthocyanins contents were determined by Folin-Ciocalteau and differential pH methods, respectively. Antioxidant activity was measured by FRAP, ORAC and DPPH methods. Antiproliferative effect was determined by sulforhodamine colorimetric method and apoptosis was analyzed by flow cytometry using propidium iodide/Annexin-V. Mitochondrial potential was evaluated using DIOC6 and ROS levels were measured by 2,7-Dicholorodihydrofluorescein diacetate (DCFH-DA). RESULTS: The total phenol and anthocyanin content were 4409.78± 63,05 mg equivalents of gallic acid/100 mL and 106,57± 1.43 mg equivalents of cyanidin-3-glycoside/100 mL, respectively. Andean berry extract showed antioxidant activity by FRAP, ORAC and DPPH methods and antiproliferative effect on SW480 and SW620 cells. It was observed a cell cycle arrest at S and G2/M phases on SW480 and at G0/G1 phase on SW620 cells. Aqueous extract did not induce mitochondrial depolarization or affect intracellular ROS levels. CONCLUSIONS: Andean berry aqueous extract has antioxidant capacity and induces apoptosis involving cell cycle arrest in SW480 and SW620 cells without mitochondrial damage.

The NF-κB Nucleolar Stress Response Pathway.

The nuclear organelle, the nucleolus, plays a critical role in stress response and the regulation of cellular homeostasis. P53 as a downstream effector of nucleolar stress is well defined. However, new data suggests that NF-κB also acts downstream of nucleolar stress to regulate cell growth and death. In this review, we will provide insight into the NF-κB nucleolar stress response pathway. We will discuss apoptosis mediated by nucleolar sequestration of RelA and new data demonstrating a role for p62 (sequestosome (SQSTM1)) in this process. We will also discuss activation of NF-κB signalling by degradation of the RNA polymerase I (PolI) complex component, transcription initiation factor-IA (TIF-IA (RRN3)), and contexts where TIF-IA-NF-κB signalling may be important. Finally, we will discuss how this pathway is targeted by aspirin to mediate apoptosis of colon cancer cells.

Anticancer Activities of Biogenic Silver Nanoparticles Targeting Apoptosis and Inflammatory Pathways in Colon Cancer Cells

Anticancer Activities of Biogenic Silver Nanoparticles Targeting Apoptosis and Inflammatory Pathways in Colon Cancer Cells

The Pivotal Role of PAO in CDK Inhibitors (Roscovitine and Purvalanol)- Triggered Apoptosis in PUMA Null HCT116 Colon Cancer Cells

Background: Cycline-dependent kinase inhibitors (CDKi); roscovitine and purvalanol, are promising anti-cancer drugs due to their strong anti-proliferative effectiveness due to activation of PA catabolism. Besides transforming acetylated spermine and spermidine into spermidine and putrescine, respectively, polyamine oxidase (PAO) also generates hydrogen peroxide in high concentrations as a by-product. PAO was assumed as a pivotal key molecule during drug-induced apoptosis in cancer cells. Our aim is to reveal the role of PAO action in CDKi-triggered apoptosis in Puma knock-out HCT116 colon cancer cells. Methods: HCT116 wt and HCT116 Puma-/- cells were treated with Roscovitine and Purvalanol and cell viability and apoptosis were determined. Protein was isolated from treated and untreated cells and key molecules of cell cycle control and polyamine pathways were investigated at translational level. Polyamine content was determined by HPLC for all conditions. MDL-72527 was used as a PAO inhibitor and apoptotic cell death was analysed. Results: Roscovitine and purvalanol induced apoptosis and increased the cytotoxic responses in HCT116 wt and HCT116 Puma-/- colon carcinoma cell lines by modulating CDK1, 4, cyclin-B1, D3. Both, CDKi altered intrinsic apoptotic pathways in HCT116 wt. Whereas, drug-induced apoptosis occurred caspase-independent in Puma-/- colon cancer cells. Roscovitine and purvalanol up-regulated polyamine catabolic enzymes, whereas CDK inhibitors decreased the polyamine levels in HCT116 wt and HCT116 Puma-/- colon cancer cells. In addition, PAO inhibitor MDL72527 prevented drug-induced apoptosis. Conclusion: PAO expression profile might be a critical target in CDK inhibitors-triggered apoptosis in HCT116 colorectal cancer cells. Thus, MAPK signaling pathway relations with cell cycle and polyamine catabolic pathway investigations are in progress.

Ginkgolide C promotes apoptosis and abrogates metastasis of colorectal carcinoma cells by targeting Wnt/β-catenin signaling pathway.

Ginkgolide C (GGC), isolated from Ginkbiloba, has been reported to display various pharmacological actions, although, anti-cancer effect of GGC has been poorly understood till now. This study aimed to investigate whether GGC can exhibit anti-neoplastic effects against colon cancer cells and explore underlying mechanism. The Wnt/β-catenin signaling can regulate cell proliferation, survival, metastasis, and migration. Wnt/β-catenin signaling pathway plays important role in colorectal cancer (CRC) and acts as a potential therapeutic target. Abnormal activation of this signaling cascades has been reported in colon CRC. We found that GGC down-regulated Wnt/β-catenin signaling cascade. GGC inhibited the expression of Wnt3a, β-catenin, and β-catenin down-stream signals (Axin-1, p-GSK3β, and β-TrCP). Also, GGC suppressed the expression of Wnt/β-catenin pathway target genes including c-myc, cyclin D1, and survivin. Additionally, GGC induced apoptosis and suppressed cell proliferation, invasion, and migration. GGC down-regulated the expressions of matrix metalloproteinase (MMP)-9 and MMP-2 proteins. Moreover, silencing of β-catenin by small interfering RNA (siRNA) enhanced the GGC-induced apoptosis and inhibitory action of GGC on invasion. Overall, our results indicate that GGC can reduce proliferation and promote apoptosis in colon cancer cells through inhibition of the Wnt/β-catenin signaling pathway. Thus, GGC can serve as a potent therapeutic agent for management of colon cancer as a novel wnt signaling inhibitor.

The upregulation of PYCR2 is associated with aggressive colon cancer progression and a poor prognosis

PYCR2 has previously been shown to be related to a range of malignancies including hepatocellular carcinoma and melanoma, but its mechanistic functions and prognostic relevance in colon cancer patients remain to be defined. Herein, we used the Oncomine, Human Protein Atlas, The Cancer Genome Atlas (TCGA), and UALCAN databases to explore the expression of this gene in different human cancer, after which the relationship between PYCR2 expression and patient clinicopathologic characteristics was evaluated. We utilized an in vitro approach to evaluate the association between PYCR2 expression and colon cancer cell proliferation, migration, invasion, and tumor microsphere formation. The cell apoptosis was analyzed by flow cytometry. Gene set enrichment analysis (GSEA) approaches were additionally used to probe signaling pathways related to PYCR2. These analyses confirmed that PYCR2 was upregulated in several cancer types including colon cancer, with such upregulation correlating with a poor patient prognosis and with malignant clinicopathological characteristics. PYCR2 expression was identified as an independent predictor of colon cancer patients’ survival, and in vitro analyses suggested that knocking down this gene was sufficient to disrupt the proliferative, migratory, invasive, and microsphere formation activities of colon cancer cells. Moreover, shPYCR2 transfection induced colon cancer cell apoptosis. GSEA suggested that high PYCR2 expression correlates with the differential enrichment of the Wnt β-catenin signaling, MYC targets, RNA polymerase, and Notch signaling pathways. Overall, these data indicate that PYCR2 is an important mediator of tumor progression and metastasis, and suggest that it may be a valuable prognostic indicator for colon cancer patient evaluation.

Transcriptome analysis upon potassium usnate exposure reveals ATF3-induced apoptosis in human gastric and colon cancer cells

BackgroundPotassium usnate (KU), a water-soluble form of usnic acid, shows anticancer activity. However, the underlying mechanisms have not been fully elucidated. PurposeWe aimed to identify the pathways involved in anticancer effects of KU in human gastric cancer (GC) and colorectal cancer (CRC) cells using RNA-sequencing (RNA-seq) based transcriptome analysis. Study DesignWe analyzed the cytotoxic effects of KU to identify the common molecular events in GC and CRC cells upon KU exposure using unbiased approaches. MethodsCell viability assays and western blot experiments were used to examine apoptotic changes, cell cycle arrest, and endoplasmic reticulum (ER) stress-induced cellular responses in KU-treated cells. Total RNA from KU-treated human GC and CRC cells was prepared for RNA-seq analysis. Gene ontology term and gene set enrichment analyses were used to identify the key mediators of the cytotoxic effects of KU. The expression of ER stress-induced apoptotic markers was evaluated using quantitative reverse-transcription PCR and western blot analysis. Chromatin immunoprecipitation assays for ATF3 and H3K27ac, and ATF3 knockdown were employed to verify the underlying molecular mechanisms. The inhibitory effect of KU on tumor growth in vivo was validated with metastatic tumor nodule formations in a mouse liver model. ResultsKU exerted cytotoxicity in human GC and CRC cells through the activation of the ER stress-induced apoptotic pathway. KU stimulated ATF3 expression, an important mediator of molecular events of apoptosis. ATF3 binds to the promoter region of ATF3, CHOP, GADD34, GADD45A, DR5, and PUMA genes and subsequently promoted apoptotic events. Knockdown of ATF3 significantly reduced the expression of ATF3 target genes and the cytotoxic effects of KU. The intraperitoneal injection of KU induced ATF3 and the apoptosis of implanted colon cancer cells, resulting in reduced metastatic tumor growth in the mouse livers. ConclusionKU exerts cytotoxic effects in human GC and CRC cells by triggering ER stress-induced apoptosis via an ATF3 dependent pathway.

Metabolomic Characterization of a cf. Neolyngbya Cyanobacterium from the South China Sea Reveals Wenchangamide A, a Lipopeptide with In Vitro Apoptotic Potential in Colon Cancer Cells.

Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC50 = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues.

Oleanolic Acid Induces Autophagy and Apoptosis via the AMPK-mTOR Signaling Pathway in Colon Cancer.

Aims The purpose of this study was to explore the biological functions of the mTOR and AMPK signaling pathways in colon cancer (CC). The potential molecular mechanisms by which oleanolic acid (OA) induces autophagy and apoptosis were also investigated. Methods The biological functions of mTOR were analyzed by GeneCards, the Search Tool for the Retrieval of Interacting Genes (STRING), and the Database for Annotation, Visualization and Integrated Discovery (DAVID). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to obtain prognostic and survival data of CC patients from the Gene Expression Omnibus (GEO) database. The effects of OA on the CC cell lines HCT-116 and SW-480 were analyzed by CCK-8, colony formation assay, and high-content system (HCS) array scan. The apoptosis rate of SW-480 and HCT-116 cells was detected by flow cytometry. The mRNA and protein expression levels in HCT-116 and SW-480 cells and NCM-460 normal colonic epithelial cells were detected by RT-PCR and Western blotting. Results mTOR was highly expressed in CC patients and acted as an oncogene. The AMPK signaling pathway mediated by mTOR predicted the poor prognosis of CC patients. OA effectively inhibited the proliferation and viability of CC cells. Furthermore, the apoptosis rate of CC cells was clearly increased following OA administration. Regarding the molecular mechanism of OA, the results indicated that mTOR and the antiapoptosis gene Bcl-2 were downregulated by OA. In addition, regulator genes of autophagy and apoptosis, including BAX, caspase-9, caspase-8, and caspase-3, were significantly upregulated by OA. Moreover, OA upregulated AMPK and its downstream proteins, including TSC2, BAX, Beclin 1, LC3B-II, and ULK1, to induce autophagy and apoptosis in CC cells. Conclusion The findings from this study demonstrate that OA could effectively inhibit the proliferation and viability of CC cells. The anti-CC activity of OA is closely related to the activation of the AMPK-mTOR signaling pathway. Activation of AMPK and inhibition of mTOR are involved in the induction of autophagy and apoptosis by OA. OA induced autophagy and apoptosis mainly in an AMPK activation-dependent manner in CC cells.

Evaluation of the anticancer activity of singly and doubly modified analogues of C20-epi-salinomycin

In developed countries, cancer is the second leading cause of death, with colon and prostate cancer belonging to the group of most often diagnosed types of neoplastic diseases. The search for new treatment strategies against these types of cancer is thus of top current interest. In this context, salinomycin (SAL), a naturally occurring polyether ionophore, has been identified recently as a very promising anticancer drug candidate towards several tumour cells. In the present work, a broad library of 24 derivatives of C20-epi-salinomycin (2), including C1 singly, C20 singly and C1/C20 doubly modified analogue structures, was screened to identify compounds with improved activity against colon and prostate cancer cells. Our study demonstrated that the growth inhibitory potency of the parent compound on both primary and metastatic colon cancer cells was similar to that of the semisynthetic products derived from SAL, and simultaneously the SAL analogues showed more potent toxic action on metastatic prostate cancer cells than that of the chemically unmodified ionophore. In contrast to the widely used oncological drug doxorubicin, some of the SAL derivatives demonstrated promising anticancer activity with no toxic effects on non-tumour cells, and with more favourable cytotoxicity than that of a reference agent 5-fluorouracil. Mechanistically, the SAL analogues induced late apoptosis in colon cancer cells and necrosis in prostate cancer cells, as well as reduced secretion of interleukin 6 (IL-6) in these cells.

Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells.

The clinical efficacy of colorectal tumor treatment is restricted due to platinum agent resistance. Translesion DNA synthesis (TLS) has been shown to contribute to this resistance; however, the exact molecular mechanism remains unknown. The present study aimed to investigate the possible function of the core of the TLS polymerase mitotic arrest deficient 2 like 2 (MAD2L2) in drug sensitivity, in order to provide a treatment rationale for platinum-based chemotherapy in colon cancer. In the present study, MAD2L2 was knocked down using MAD2L2-specific small interfering (si)RNA. HCT116 and SW620 cells were treated with oxaliplatin and MG132; oxaliplatin is a platinum compound that induces DNA damage and MG132 is a potent proteasome inhibitor. Cell viability was determined using an MTT assay. Cell apoptosis was examined via flow cytometry and TUNEL assay. The activity of proteasome 26S subunit, non-ATPase 13 (PSMD13) was detected using ELISA, while the expression levels of apoptotic-related proteins were detected via western blotting. The results demonstrated that cells treated with oxaliplatin or MG132 alone had decreased viability, but a synergistic effect was not observed after co-treatment. In addition, the knockdown of MAD2L2 caused by siMAD2L2 or oxaliplatin treatment increased the expression levels of the pro-apoptotic proteins Bax and Bak and decreased the expression levels of the anti-apoptotic protein Bcl-2, compared with the negative control group. Moreover, MG132 alleviated the decrease in MAD2L2 expression, while reducing siMAD2L2-induced cell apoptosis. These results indicate that oxaliplatin promotes siMAD2L2-induced apoptosis in colon cancer cells. This process was associated with the Bcl-2 and ubiquitin-proteasome pathway. Overall, the present study provides a theoretical basis for improving the clinical efficacy of colon cancer by combining chemotherapy and gene therapy.

Effects of miR-335-5p targeting G6PD on proliferation and apoptosis of colon cancer cells

Objective: To investigate the effects of miR-335-5p targeting glucose-6-phosphate dehydrogenase (G6PD) on the proliferation and apoptosis of colon cancer cells. Methods: Normal colon cell group, blank control group, NC group and miRNA-335-5p mimic group were set up. Colonic epithelial cells (IEC) and human colon cancer cells SW480 were cultured in vitro, and the cells in the NC group and miRNA-335-5p mimic group cells were transfected. RT-qPCR was used to detect the expression levels of miR-335-5p and G6PD mRNA in each group of cells. The targeting effect of miR-335-5p on G6PD was verified by Double Luciferase Report experiment. MTT assay was used to detect cell proliferation. Flow cytometry was used to detect the apoptosis rate. The expressions of G6PD, Bax, Bcl-2 and caspase-3 were detected by Western blot. Results: Compared with normal colon cells, the relative expression levels of miR-335-5p in SW480 cells of colon cancer in the blank control group and NC group were decreased, and the relative expression level of G6PD mRNA was increased (P＜0.05); compared with the blank control group and NC group, the expression level of miR-335-5p in miR-335-5p mimic group was increased significantly, and the expression of G6PD mRNA was decreased significantly (P＜0.05). Compared with the blank control group and NC group, the proliferative activity of colon cancer SW480 cells in miR-335-5p mimic group was decreased significantly, and the apoptosis rate was increased significantly (P＜0.05). The relative activity of luciferase in miR-335-5p mimic + WT-G6PD 3 '- UTR group was lower than that in miR-335-5p NC + WT-G6PD 3' - UTR group (P＜0.05). Compared with the blank control group, the relative expression levels of G6PD and bcl-2 protein in miR-335-5p mimic group were decreased significantly, and the expression levels of Bax and caspase-3 protein were increased significantly (P＜0.05). Conclusion: MiR-335-5p may inhibit the proliferation and promote apoptosis of colon cancer cells by targeting G6PD.

Abstract 1069: Determining the effect of bazedoxifene in combination with chemotherapy on colon cancer cells

Abstract Inflammatory cytokines, such as interleukin-6 (IL-6) and IL-11, activate the signal transducer and activator of transcription 3 (STAT3), which drives the gene transcription of cellular processes attributed as hallmarks of cancer. High levels of these cytokines, in combination with driver mutations, facilitate tumour growth and progression in preclinical models of colon cancer. Previous studies in our laboratory identified bazedoxifene (BZA), currently approved for the treatment of osteoporosis, as a small molecule inhibitor of GP130 (the receptor common to the IL-6 family of cytokines), selectively suppressing IL-6 and IL-11 signalling to reduce colon and gastric cancer growth in vivo (Thilakasiri et al. EMBO Mol Med 2019). The aim of this study is to determine the key cellular mechanisms influenced by GP130 inhibition to mediate anti-tumour effects in colon cancer cells. Additionally, we assessed the combined effects of BZA with standard of care chemotherapy drugs on cell proliferation and apoptosis. Using LIM2405 and HT29 colon cancer cells, the combined effect of BZA, fluorouracil and oxaliplatin on inducing apoptosis in LIM2405 and HT29 colon cancer cells was analysed using flow cytometry and confirmed using Western blotting and DIC microscopy. The effects of BZA was further analysed on HT29 xenograft growth and metastasis in vivo. Levels of STAT3 activation in response to IL-11/STAT3 signalling was characterised by Western blotting. Our results demonstrated that combination treatment with BZA, fluorouracil and oxaliplatin significantly increased apoptosis in LIM2405 cells and BZA significantly induced apoptosis in HT29 cells. Our data showed that BZA inhibited GP130-dependent STAT3 activity in the human colon cancer cell line LIM2405 and HT29. BZA treatment sensitized cells to chemotherapy leading to increased apoptosis. BZA treatment also reduced both primary tumour and metastatic burden in vivo demonstrating that gp130 mediated STAT3 inhibition is an attractive target for the treatment of early stage and advanced stage colon cancer. Citation Format: Rhynelle S. Dmello, Pathum Thilakasiri, Belinda Duscio, Ivan Poon, Matthias Ernst, Ashwini Chand. Determining the effect of bazedoxifene in combination with chemotherapy on colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1069.

Seaweed Components as Potential Modulators of the Gut Microbiota.

Macroalgae, or seaweeds, are a rich source of components which may exert beneficial effects on the mammalian gut microbiota through the enhancement of bacterial diversity and abundance. An imbalance of gut bacteria has been linked to the development of disorders such as inflammatory bowel disease, immunodeficiency, hypertension, type-2-diabetes, obesity, and cancer. This review outlines current knowledge from in vitro and in vivo studies concerning the potential therapeutic application of seaweed-derived polysaccharides, polyphenols and peptides to modulate the gut microbiota through diet. Polysaccharides such as fucoidan, laminarin, alginate, ulvan and porphyran are unique to seaweeds. Several studies have shown their potential to act as prebiotics and to positively modulate the gut microbiota. Prebiotics enhance bacterial populations and often their production of short chain fatty acids, which are the energy source for gastrointestinal epithelial cells, provide protection against pathogens, influence immunomodulation, and induce apoptosis of colon cancer cells. The oral bioaccessibility and bioavailability of seaweed components is also discussed, including the advantages and limitations of static and dynamic in vitro gastrointestinal models versus ex vivo and in vivo methods. Seaweed bioactives show potential for use in prevention and, in some instances, treatment of human disease. However, it is also necessary to confirm these potential, therapeutic effects in large-scale clinical trials. Where possible, we have cited information concerning these trials.

MiRNA Profile and Bioinformatic Analysis for Diagnosis in Patients with Stage IIIA Colon Cancer.

Early diagnosis is a critical factor in deciding the outcome of colon cancer, as is the case with other types of cancers. Recent scientific developments have enabled the use of biomarkers for diagnosis and for designing treatment strategies for various cancer types. Further, identification of potential targets of these biomarkers will facilitate a better understanding of molecular processes. The aim of this study is to analyze microRNA expression profile, and through bioinformatic analyses determine the cellular processes of potential target genes and understand their molecular mechanism in stage IIIA colon cancer patients. The microRNA expression profiles of both normal and tumor tissues of seven patients were analyzed using the Affymetrix microarray system. The target genes were identified by performing a KEGG pathway analysis on eight miRNAs (hsa-miR-362-3p, hsa-miR-34c-5p, hsa-miR-34c-3p, hsa-miR-34a-3p, hsa-miR-19b-1-3p, hsa-miR-371a-5p, hsa-miR-941 ad hsa-miR-7-5p), which were selected through an array scan by using DIANA-miRPath v.3 bioinformatic analysis tool. Biological pathway and cellular component analyses were performed on 30 genes targeted by miRNAs using FunRich Gene Enrichment tool. These analyses indicated that the genes targeted by these eight miRNAs played a role in either cell communication (53%), signal transduction (60%) or apoptosis (20%) in stage IIIA colon cancer. Taken together, these data suggest that these miRNAs can be used as biomarkers in Stage IIIA colon cancer.

The Novel Curcumin Derivative 1g Induces Mitochondrial and ER-Stress-Dependent Apoptosis in Colon Cancer Cells by Induction of ROS Production.

Reactive oxygen species (ROS) play an important role in cellular metabolism. Many chemotherapeutic drugs are known to promote apoptosis through the production of ROS. In the present study, the novel curcumin derivative, 1g, was found to inhibit tumor growth in colon cancer cells both in vitro and in vivo. Bioinformatics was used to analyze the differentially expressed mRNAs. The mechanism of this effect was a change in mitochondrial membrane potential caused by 1g that increased its pro-apoptotic activity. In addition, 1g produced ROS, induced G1 checkpoint blockade, and enhanced endoplasmic reticulum (ER)-stress in colon cancer cells. Conversely, pretreatment with the ROS scavenging agent N-acetyl-l-cysteine (NAC) inhibited the mitochondrial dysfunction caused by 1g and reversed ER-stress, cell cycle stagnation, and apoptosis. Additionally, pretreatment with the p-PERK inhibitor GSK2606414 significantly reduced ER-stress and reversed the apoptosis induced by colon cancer cells. In summary, the production of ROS plays an important role in the destruction of colon cancer cells by 1g and demonstrates that targeted strategies based on ROS represent a promising approach to inhibit colon cancer proliferation. These findings reveal that the novel curcumin derivative 1g represents a potential candidate therapeutics for the treatment of colon cancer cells, via apoptosis caused by mitochondrial dysfunction and endoplasmic reticulum stress.

Study on effects of miR-141-3p in proliferation, migration, invasion and apoptosis of colon cancer cells by inhibiting Bcl2.

This study aimed to investigate the relationship between miR-141-3p and B lymphocyte-2 gene (Bcl2) gene and its biological behavior on colon cancer cell line SW480. qRT-PCR was used to detect the expression level of miR-141-3p in colon cancer tissues and adjacent tissues, as well as in colon cancer cell line and normal human colonic epithelial cell line FHC. MTT assay, wound assay, and Transwell demonstrated the effects of miR-141-3p on colon cancer proliferation, migration and invasion. Targetscan7.1 predictive software and dual luciferase reporter assays were used to detect the targeted regulation of miR-141-3p on the apoptosis-related gene Bcl2. MTT assay, wound assay, Transwell and flow cytometry were used to detect the effect of Bcl2 on miR-141-3p on colon cancer proliferation, migration, invasion and apoptosis. Compared with adjacent tissues, the expression of miR-141-3p in colon cancer tissues was significantly down-regulated. Colon cancer patients with low expression of miR-141-3p had poorer prognosis. Compared with normal colonic epithelial cells, miR-141-3p expression was significantly down-regulated in colon cancer cell lines, and overexpression of miR-141-3p significantly attenuated the proliferation, migration and invasion of colon cancer cells. Knockdown of miR-141-3p significantly promoted the proliferation, migration and invasion of colon cancer cells. miR-141-3p targets the negative regulation of Bcl2. Knockdown of Bcl2 significantly attenuated the promotion of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells and inhibition of apoptosis. Knockdown of Bcl2 significantly enhanced the inhibition effect of miR-141-3p inhibitor on proliferation, migration and invasion of colon cancer cells. In conclusion, miR-141-3p can inhibit the cancer by regulating Bcl2, and miR-141-3p has the potential to become a potential therapeutic target for colon cancer.

Autophagy Induction by Trichodermic Acid Attenuates Endoplasmic Reticulum Stress-Mediated Apoptosis in Colon Cancer Cells.

Colorectal cancer (CRC) is the third leading malignant tumor in the world, which has high morbidity and mortality. In this study we found that trichodermic acid (TDA), a secondary metabolite isolated from the plant endophytic fungus Penicillium ochrochloronthe with a variety of biological and pharmacological activities, exhibited the antitumor effects on colorectal cancer cells in vitro and in vivo. Our results showed that TDA inhibited the proliferation of colon cancer cells in a dose-dependent manner. TDA induces sustained endoplasmic reticulum stress, which triggers apoptosis through IRE1α/XBP1 and PERK/ATF4/CHOP pathways. In addition, we found that TDA mediated endoplasmic reticulum stress also induces autophagy as a protective mechanism. Moreover, combined treatment of TDA with autophagy inhibitors significantly enhanced its anticancer effect. In conclusion, our results indicated that TDA can induce ER stress and autophagy mediated apoptosis, suggesting that targeting ER stress and autophagy may be an effective strategy for the treatment of CRC.

Effect of RNF152 on NO induced apoptosis of colon cancer cells

Objective: To investigate the role and mechanism of ring finger protein 152 (RNF152) in the development of colitis-associated colon cancer (CAC). Methods: CAC was induced by azoxymethane (AOM) and dextran sulfate sodium (DSS) in C57BL/6 mice. Three different stages of mice during the development of colon cancer were obtained, named AD1, AD2 and AD3, respectively. A control group of mice without any treatment was set up as well. The expression of RNF152 in mouse colon tissues was measured by real-time quantitative polymerase chain reaction (RT-qPCR). The effects of RNF152 overexpression on apoptosis and nitric oxide (NO) induced apoptosis was examined by flow cytometry. The expressions of Bcl-2 and Bcl-XL were detected by western blot. Results: CAC was effectively induced by AOM and DSS in C57BL/6 mice. The tumor incidence rate of AD3 group was 100%. The whole genome expression microarray data from mouse AOM-DSS model indicated that the mRNA level of RNF152 was gradually decreased during the development of colon cancer. The RT-qPCR results showed that RNF152 mRNA level in AD3 was 1.23±0.18, higher than 0.52±0.08 in negative control (P<0.01). Flow cytometry analysis showed that overexpression of RNF152 increased the apoptosis of RKO cells (P<0.01). The apoptotic rate of RKO-RNF152 cells treated with NO donor DETA NONOate was (31.2±3.1)%, higher than (14.2±2.1)% in RKO-PCDB cells (P<0.001). Overexpression of RNF152 significantly decreased the protein expressions of Bcl-XL and Bcl-2. Conclusion: Downregulation of RNF152 may facilitate the development of CAC by inhibiting the cell apoptosis.

Verbesina encelioides-induced cytotoxicity and mitochondria-mediated apoptosis in human colon cancer cells through ROS generation

Verbesina encelioides-induced cytotoxicity and mitochondria-mediated apoptosis in human colon cancer cells through ROS generation