HT-29 Colorectal Cancer Cells Research Articles

Folic acid conjugated capecitabine capped green synthesized fluorescent carbon dots as a targeted nano-delivery system for colorectal cancer

Herein, we have developed folic acid conjugated capecitabine capped passivated carbon dots (CAP-FA-CDPs) for colorectal cancer targeting. Carbon dots were synthesized via a microwave treatment of the Buchnania lanzan leaf extract and PEG 6000 was used as a surface passivating agent. The developed system has shown an acidic pH (pH 5.0) dependent drug release of 84.57% after 72 h. In an in vitro cytotoxicity study, CDPs showed almost no toxicity to the HT-29 colorectal cancer cells with the viability rate of 96.03%. However, the viability of HT-29 cells significantly dropped to 24.4% in CAP-FA-CDPs treated group only after 36 h of incubation. A cellular uptake study showed an efficient internalization of CAP-FA-CDPs systems by HT-29 cells expected via folic acid-folate receptor (ligand-receptor) interactions. Greater reactive oxygen species (ROS) generation further confirmed the successful cellular uptake of the CAP-FA-CDPs. Finally, flow cytometry analysis clearly showed the apoptotic potential of the CAP-FA-CDPs conjugated system on HT-29 cells where live cells significantly decreased to 21.4% and apoptotic cells increased to 77.2%. Thus, the presently developed CAP-FA-CDPs nano delivery system offers a promising strategy for targeted and effective drug delivery in colorectal cancer. • Folic acid conjugated capecitabine capped CDs synthesized via microwave method. • Efficient internalization of CAP-FA-CDPs inside HT-29 cancer cells was seen. • In cytotoxicity study, CAP-FA-CDPs dropped HT-29 cancer cells count to 24.4%. • In FACS, apoptotic cells count was found 77.2% in CAP-FA-CDPs treated HT-29 cells.

An Efficient and Quick Analytical Method for the Quantification of an Algal Alkaloid Caulerpin Showed In-Vitro Anticancer Activity against Colorectal Cancer.

Biological invasion is the successful spread and establishment of a species in a novel environment that adversely affects the biodiversity, ecology, and economy. Both invasive and non-invasive species of the Caulerpa genus secrete more than thirty different secondary metabolites. Caulerpin is one of the most common secondary metabolites in genus Caulerpa. In this study, caulerpin found in invasive Caulerpa cylindracea and non-invasive Caulerpa lentillifera extracts were analyzed, quantified, and compared using high-performance thin layer chromatography (HPTLC) for the first time. The anticancer activities of caulerpin against HCT-116 and HT-29 colorectal cancer (CRC) cell lines were also tested. Caulerpin levels were found higher in the invasive form (108.83 ± 5.07 µg mL-1 and 96.49 ± 4.54 µg mL-1). Furthermore, caulerpin isolated from invasive Caulerpa decreased cell viability in a concentration-dependent manner (IC50 values were found between 119 and 179 µM), inhibited invasion-migration, and induced apoptosis in CRC cells. In comparison, no cytotoxic effects on the normal cell lines (HDF and NIH-3T3) were observed. In conclusion, HPTLC is a quick and novel method to investigate the caulerpin levels found in Caulerpa extracts, and this paper proposes an alternative utilization method for invasive C. cylindracea due to significant caulerpin content compared to non-invasive C. lentillifera.

3D bioprinted colorectal cancer models based on hyaluronic acid and signalling glycans

In cancer microenvironment, aberrant glycosylation events of ECM proteins and cell surface receptors occur. We developed a protocol to generate 3D bioprinted models of colorectal cancer (CRC) crosslinking hyaluronic acid and gelatin functionalized with three signalling glycans characterized in CRC, 3′-Sialylgalactose, 6′-Sialylgalactose and 2′-Fucosylgalactose. The crosslinking, performed exploiting azide functionalized gelatin and hyaluronic acid and 4arm-PEG-dibenzocyclooctyne, resulted in biocompatible hydrogels that were 3D bioprinted with commercial CRC cells HT-29 and patient derived CRC tumoroids. The glycosylated hydrogels showed good 3D printability, biocompatibility and stability over the time. SEM and synchrotron radiation SAXS/WAXS analysis revealed the influence of glycosylation in the construct morphology, whereas MALDI-MS imaging showed that protein profiles of tumoroid cells vary with glycosylation, indicating that sialylation and fucosylation of ECM proteins induce diverse alterations to the proteome of the tumoroid and surrounding cells.

Modulatory Effect of Chlorogenic Acid and Coffee Extracts on Wnt/β-Catenin Pathway in Colorectal Cancer Cells.

The Wnt/β-Catenin pathway alterations present in colorectal cancer (CRC) are of special interest in the development of new therapeutic strategies to impact carcinogenesis and the progression of CRC. In this context, different polyphenols present in natural products have been reported to have modulatory effects against the Wnt pathway in CRC. In this study, we evaluate the effect of two polyphenol-rich coffee extracts and chlorogenic acid (CGA) against SW480 and HT-29 CRC cells. This involved the use of MTT and SRB techniques for cell viability; wound healing and invasion assay for the evaluation of the migration and invasion process; T cell factor (TCF) reporter plasmid for the evaluation of transciption factor (TCF) transcriptional activity; polymerase chain reaction (PCR) of target genes and confocal fluorescence microscopy for β-Catenin and E-Cadherin protein fluorescence levels; and subcellular localization. Our results showed a potential modulatory effect of the Wnt pathway on CRC cells, and we observed a reduction in the transcriptional activity of β-catenin. All the results were prominent in SW480 cells, where the Wnt pathway deregulation has more relevance and implies a constitutive activation of the signaling pathway. These results establish a starting point for the discovery of a mechanism of action associated with these effects and corroborate the anticancer potential of polyphenols present in coffee, which could be explored as chemopreventive molecules or as adjunctive therapy in CRC.

Schwann cells promote the migration and invasion of colorectal cancer cells via the activated NF-κB/IL-8 axis in the tumor microenvironment.

Evidence has shown neurons and glial cells were closely related to tumor progression. As the predominant glial cells in the external innervated nerves of the gastrointestinal, the role of Schwann cells (SCs) in colorectal cancer (CRC) has not been well explored. HCT-116 and HT-29 CRC cells were treated with conditioned medium (CM) from SCs, and the cells' proliferative and migrating capacities were examined. Cytokine array analysis was used to identify the tumor-promoting-cytokines from SCs-CM. Molecular changes from SCs after being co-cultured with tumor cells were detected by ELISA and reverse transcription-quantitative PCR. The activation of the nuclear factor kappa B (NF-κB) signaling pathway in SCs was demonstrated by immunofluorescence staining. Neutralizing antibody was used to verify the tumor-promoting effects of key cytokine. Migration and invasion of CRC cells were markedly aided by CM from SCs in vitro. Interleukin-8 (IL-8) was identified as an effective factor. SCs co-cultured with CRC cells upregulated IL-8 expression, which may be related to its activated NF-κB signaling pathway. Neutralization of IL-8 attenuated the tumor-promoting effect of SCs. The present study identified a new mechanism of tumor-neuroglia interaction, enriching the concept of the tumor-neural axis in the tumor microenvironment of CRC, which also inspired potential targets for anti-cancer therapies.

Zinc Acts Synergistically with Berberine for Enhancing Its Efficacy as an Anti-cancer Agent by Inducing Clusterin-Dependent Apoptosis in HT-29 Colorectal Cancer Cells.

It is now widely accepted that anti-cancer medications are most effective when administered in combination. Zinc is an essential micronutrient whilst berberine is a well-known natural phytochemical, both having multiple molecular mechanisms of action. The present study aimed to determine the combinatorial effect of zinc and berberine on the human adenocarcinoma HT-29 cancer cell line. The anti-proliferative activity of berberine and zinc was determined by cell viability and colony-forming assays. The combination index and drug reduction index values of zinc and berberine co-treatments were estimated by suitable software. Flow cytometry was used to analyse cell cycle distribution and Annexin V/PI staining. The expression of apoptosis and zinc signalling markers were analysed by RT-qPCR and immunoblot analysis. Berberine decreased the viability of colon cancer cells in a dose-dependent manner whilst zinc alone had no significant influence on it. However, zinc and berberine co-treatment resulted in a synergistic anti-cancer action which was demonstrated by G2/M phase arrest of cell growth at a lower dose of berberine. Annexin V assay demonstrated that the synergistic impact of zinc and berberine boosted the number of apoptotic cells. Gene expression analysis at both transcriptional and translational levels showed the upregulation of apoptotic (caspase-3 and caspase-8) and a zinc-sensing receptor (GPR39) gene with concomitant downregulation of anti-apoptotic genes like proliferating cell nuclear antigen (PCNA) and clusterin. Our findings showed that the combination of zinc and berberine has synergistic anti-cancer efficacy and thus could be used as a potential chemopreventive option for colon cancer.

Arecaceae fruits: Fatty acids, phenolic compounds and in vitro antitumor activity

Arecaceae fruits are regarded as raw sources of valuable phytochemicals. In this work, several Arecaceae fruits belonging to eleven taxa were screened for fatty acids (FA) by gas chromatography with flame ionization detector and checked for their in vitro antitumor activity against the HT-29 colorectal cancer cells line through the MTT test. The parallel use of two chromatography systems, HPLC-DAD and LC-MS, allowed the precise characterization of all phenolic compounds contained in the fruits. Howea belmoreana had the highest FA amounts (11.7 g/100 g on dry weight); Syagrus romanzoffiana had a relatively high PUFA content (26.3% of total FA); and Butia capitata contains high amounts of medium-chain saturated FA (51.2%). Total phenolics reached 201.8 mg/100 g on dry weight in Phoenix dactylifera var. Medjool. Among phenolics, occurred benzoic acids, phenylpropanoic acid, and cinnamic acid derivatives. It highlights the great diversity of flavonoids detected as (−)-catechin, quercetin, and kaempferol, as well as phenolic glycosides, such as isorhamnetin-3-O-glucoside. The methanol:water (60:40, v/v) extracts of fruits induced dose- and time-dependent inhibitory effects on HT-29 cancer cells. Overall, the fruits of Arecaceae taxa evaluated here constitute suitable candidates to be used as functional foods.

Isothiocyanate-Rich Extracts from Cauliflower (Brassica oleracea Var. Botrytis) and Radish (Raphanus sativus) Inhibited Metabolic Activity and Induced ROS in Selected Human HCT116 and HT-29 Colorectal Cancer Cells

Cruciferous vegetables such as cauliflower and radish contain isothiocyanates exhibiting chemoprotective effects in vitro and in vivo. This research aimed to assess the impact of cauliflower (CIE) and radish (RIE) isothiocyanate extracts on the metabolic activity, intracellular reactive oxygen species (ROS), and LDH production of selected human colorectal adenocarcinoma cells (HCT116 and HT-29 for early and late colon cancer development, respectively). Non-cancerous colon cells (CCD-33Co) were used as a cytotoxicity control. The CIE samples displayed the highest allyl isothiocyanate (AITC: 12.55 µg/g) contents, whereas RIE was the most abundant in benzyl isothiocyanate (BITC: 15.35 µg/g). Both extracts effectively inhibited HCT116 and HT-29 metabolic activity, but the CIE impact was higher than that of RIE on HCT116 (IC50: 0.56 mg/mL). Assays using the half-inhibitory concentrations (IC50) of all treatments, including AITC and BITC, displayed increased (p < 0.05) LDH (absorbance: 0.25-0.40 nm) and ROS release (1190-1697 relative fluorescence units) in both cell lines. BITC showed the highest in silico binding affinity with all the tested colorectal cancer molecular markers (NF-kB, β-catenin, and NRF2-NFE2). The theoretical evaluation of AITC and BITC bioavailability showed high values for both compounds. The results indicate that CIE and RIE extracts display chemopreventive effects in vitro, but additional experiments are needed to validate their effects.

Multi-glycomic analysis of spheroid glycocalyx differentiates 2- and 3-dimensional cell models.

A multi-glycomic method for characterizing the glycocalyx was employed to identify the difference between 2-dimensional (2D) and 3-dimensional (3D) culture models with two human colorectal cancer cell lines, HCT116 and HT29. 3D cell cultures are considered more representative of cancer due to their ability to mimic the microenvironment found in tumors. For this reason, they have become an important tool in cancer research. Cell-cell interactions increase in 3D models compared to 2D, indeed significant glycomic changes were observed for each cell line. Analyses included the N-glycome, O-glycome, glycolipidome, glycoproteome, and proteome providing the most extensive characterization of the glycocalyx between 3D and 2D thus far. The different glycoconjugates were affected in different ways. In the N-glycome, the 3D cells increased in high-mannose glycosylation and in core fucosylation. Glycolipids increased in sialylation. Specific glycoproteins were found to increase in the 3D cell, elucidating the pathways that are affected between the two models. The results show large structural and biological changes between the 2 models suggesting that the 2 are indeed very different potentially affecting individual outcomes in the study of diseases.

Investigation of the effects of isoeugenol-based phenolic compounds on migration and proliferation of HT29 colon cancer cells at cellular and molecular level

Colorectal cancer is a type of cancer encountered worldwide and ranks third among all cancer types in terms of incidence. Polyphenols have been shown to have a wide range of biological functions, including a significant impact on cancer start, development, and promotion through regulating many signaling pathways. The aim of this study was to investigate the anticancer effects of isoeugenol based compounds 1, 2 on HT29 colorectal cancer cell line in vitro. MTT test and scratch assay were carried out to determine the effect of these compounds on HT29 cell proliferation and migration respectively. In addition, mRNA expression levels of apoptosis and metastasis-related genes (p53, Bcl2, Bax, Caspase 3, Caspase7, Caspase8, Caspase9, HIF1-α, VEGF, MMP-2, MMP-9) were examined by quantitative real-time PCR. The results indicated that 1 and 2 inhibited HT29 cell proliferation and induced apoptosis by increasing the Bax/Bcl2 ratio and Caspase-9 and Caspase-3 mRNA expression. In conclusion, the results of this study showed that the treatment of these compounds significantly suppressed the mRNA expressions of metastasis-related genes such as Matrix Metalloproteinase-2, Matrix Metalloproteinase-9, Vascular Endothelial Growth Factor and Hypoxia‑Inducible Factor 1α.

GPER Agonist G1 Prevents Wnt-Induced JUN Upregulation in HT29 Colorectal Cancer Cells.

Women consistently show lower incidence and mortality rates for colorectal cancer (CRC) compared to men. Epidemiological evidence supports a pivotal role for estrogen in protecting women against CRC. Estrogen protective effects in CRC have been mainly attributed to the estrogen receptor beta (ERβ) however its expression is lost during CRC progression. The role of the G-protein coupled membrane estrogen receptor (GPER/GPER1/GPR30), which remains expressed after ERβ loss in CRC, is currently under debate. We hypothesise that estrogen can protect against CRC progression via GPER by modulating the Wnt/β-catenin proliferative pathway which is commonly hyperactivated in CRC. We sought evidence of sexual dimorphism within the Wnt/β-catenin pathway by conducting Kaplan–Meier analyses based on gene expression of the Wnt receptor FZD1 (Frizzled 1) in multiple public domain CRC patient data sets. High expression of FZD1 was associated with poor relapse-free survival rates in the male but not the female population. In female-derived HT29 CRC cell lines, we show that β-catenin nuclear translocation was not affected by treatment with the GPER agonist G1. However, G1 prevented the Wnt pathway-induced upregulation of the JUN oncogene. These novel findings indicate a mechanistic role for GPER in protecting against CRC progression by selectively reducing the tumorigenic effects of hyperactive Wnt/β-catenin signalling pathways in CRC.

Synthesis and biological evaluation of thiazole and thiadiazole derivatives as potential anticancer agents

A new series of 4-methyl-2-{2-[(aryl)methylidene]hydrazinyl}-1,3-thiazole (2a-i), N-(4-acetyl-5-aryl)4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamides (3a-b) and N-(5-(4-(substituted phenyl)-1,3,4-thiadiazol-2-yl)acetamides (3c-i) were synthesized by the reaction of 2-((aryl)methylene)hydrazine-1-carbothioamides (1a-i) and acetic anhydride or chloroacetone. The cytotoxic activities of the products were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Hela cervical cancer, MCF-7 breast carcinoma and HT-29 colorectal cancer cell lines. Thiazole based compounds 2a, 2b, 2f and 2i, bearing 4-bromothiophen-2-yl, naphthalen-2-yl, 2,5-difluorophenyl and 4-(trifluoromethoxy)phenyl moieties, respectively; also N-(4-acetyl-5-(naphthalen-2-yl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)acetamide (3b) and N-(5-(2,6-difluorophenyl)-1,3,4-thiadiazol-2-yl)acetamide (3d) exhibited significant anticancer activity against three cancer cell lines. Moreover, these active compounds were further evaluated by apoptotic protein levels. The results showed that these thiazole and thiadiazole compounds induced apoptosis of cancer cells.

Mesenchymal Stem Cells Trigger Epithelial to Mesenchymal Transition in the HT-29 Colorectal Cancer Cell Line

Mesenchymal Stem Cells Trigger Epithelial to Mesenchymal Transition in the HT-29 Colorectal Cancer Cell Line

Gold Nanoparticles Synthesized with Common Mullein (Verbascum thapsus) and Castor Bean (Ricinus communis) Ethanolic Extracts Displayed Antiproliferative Effects and Induced Caspase 3 Activity in Human HT29 and SW480 Cancer Cells.

Gold nanoparticles (AuNPs) are promising nanomaterials exhibiting anti-cancer effects. Green AuNPs synthesis using plant extracts can be used to achieve stable and beneficial nanoparticles due to their content of bioactive compounds. This research aimed to synthesize and evaluate the antiproliferative and caspase-3 activity induction of green AuNPs synthesized with common mullein (V. thapsus) flowers (AuNPsME) and castor bean (R. communis) leaves (AuNPsCE) ethanolic extracts in human HT29 and SW480 colorectal cancer cells. Their effect was compared with chemically synthesized AuNPs (AuNPsCS). The extracts mainly contained p-coumaric acid (71.88–79.93 µg/g), ferulic acid (19.07–310.71 µg/g), and rutin (8.14–13.31 µg/g). The obtained nanoparticles presented typical FT-IR bands confirming the inclusion of polyphenols from V. thapsus and R. communis and spherical/quasi-spherical morphologies with diameters in the 20.06–37.14 nm range. The nanoparticles (20–200 µg/mL) showed antiproliferative effects in both cell lines, with AuNPsCE being the most potent (IC50 HT29: 110.10 and IC50SW480: 64.57 µg/mL). The AuNPsCS showed the lowest intracellular reactive oxygen species (ROS) generation in SW480 cells. All treatments induced caspase 3/7 activity to a similar or greater extent than 30 mM H2O2-treated cells. Results indicated the suitability of V. thapsus and R. communis extracts to synthesize AuNPs, displaying a stronger antiproliferative effect than AuNPsCS.

The Transcription Factor Otc4A Stimulates the Proliferation, Invasion, and Stemness of Colorectal Cancer Cells by Inhibiting the Regulation of miR-7-5p on TLR4.

Background To investigate the effects and mechanism of octamer-binding transcription factor 4 (Otc4A) on proliferation, invasion, and stemness of colorectal cancer (CRC) cells. Methods Firstly, normal fetal human cells (FHC, colon epithelial cells) and HT29 cells (CRC cells) were cultured. The expression levels of Otc4A, miR-7-5p, and TLR4 in cells were then detected by qRT-PCR. CCK-8 was adopted to measure cell proliferation rate after Otc4A, miR-7-5p, and TLR4, respectively, were either knocked out or overexpressed in HT29 cells. Later, the cell viability was detected by cell cloning assay; cell invasion by transwell; cell sphere-forming ability by sphere-formation assay; protein expression level of Otc4A, p65, p-p65, and TLR4 by western blot; and the targeting relationships between miR-7-5p and Otc4A as well as miR-7-5p and TLR4 by dual-luciferase reporter assay. Finally, chromatin immunoprecipitation was applied to verify the interaction between Otc4A and miR-7-5p. Results In HT29 cells, Otc4A expression was significantly increased. Additionally, the knockdown of Otc4A prevented HT29 cells from proliferating, migrating, forming spheres, and activating NF–B signaling. Otc4A could negatively regulate miR-7-5p, and miR-7-5p could target TLR4 expression. Besides, a negative correlation was found between Otc4A and miR-7-5p. Finally, the knockdown of miR-7-5p or overexpression of TLR4 could significantly reverse the effect of the knockdown of Otc4A on HT29 cells. Conclusion The transcription factor Otc4A can regulate the level of TLR4 by inhibiting the expression of miR-7-5p and then promote the proliferation and invasion of CRC cell HT29 as well as enhance cell stemness.

Effect of drying method on the production of in vitro short-chain fatty acids and histone deacetylase mediation of cocoa pod husk.

We evaluated the effect of cocoa pod husk (CPH) processing (microwave [MW], forced-air drying [FAD], and FAD plus extrusion [FAD-E]), and in vitro gastrointestinal digestion on the in vitro human colonic fermentation metabolism, in vitro bioactivity on human HT-29 colon cancer cell, and the in silico mechanism of selected compounds. CPH as a substrate for human colonic microbiota significantly decrease local pH (MW -0.7, FAD -0.2, and FAD-E -0.3, 24 h) and modifies their metabolic activity (short-chain fatty acids [SCFAs] production). FAD-E generated the highest butyric (7.6 mM/L, 4 h) and FAD the highest acetic and propionic acid levels (71.4 and 36.7 mM/L, 24 h). The in vitro colonic fermented FAD-E sample (FE/FAD-E) caused HT-29 colorectal cancer cells death by inducing damage on membrane integrity and inhibiting (up to 92%) histone-deacetylase (HDAC) activity. In silico results showed that chlorogenic acid, (-)-epicatechin, and (+)-catechin, followed by butyric and propionic acids, are highly involved in the HDAC6 inhibitory activity. The results highlight the potential human health postbiotic benefits of CPH consumption, mediated by colonic microbiota-derived metabolites. PRACTICAL APPLICATION: The enormous amount of CPH (10 tons/1 ton of dry beans) generated by the cocoa industry can be used as a removable source of bioactive compounds with physicochemical functionality and health bioactivity. However, their potential applications and health benefits are insufficiently explored. CPH represents a serious disposal problem; practical and innovative ideas to use this highly available and affordable material are urgent. Research exploring their potential applications can increase the sustainability of the cocoa agro-industry. This paper highlights the value addition that can be achieved with this valuable industrial co-product, generating new functional products and ingredients.

Oral delivery of camptothecin-loaded multifunctional chitosan-based micelles is effective in reduce colorectal cancer.

Colorectal cancer (CRC) is a heterogeneous disease with high incidence and mortality worldwide. The efficacy of conventional CRC chemotherapy is hampered by poor drug solubility and bioavailability and suboptimal pharmacokinetic profiles. In this work, camptothecin (CPT), a potent anticancer drug, was loaded into an amphiphilic chitosan modified with PEG and oleic acid, to reduce CRC progression after oral administration. While CPT-loaded micelles presented anticancer activity against HCT116, Caco-2 and HT29 CRC cell lines in vitro, empty micelles demonstrated a safe profile when incubated with human blood cells and colorectal cancer cell lines. In a more complex 3D CRC multicellular spheroid model, CPT-loaded micelles also exhibited a significant effect on the spheroid's metabolic activity and size reduction. Remarkably, in vivo studies performed in a HCT116 xenograft model, showed a significant reduction on the tumor growth during and after treatment with CPT-loaded micelles. Moreover, in a more biological relevant in vivo model of chemically-induced CRC, orally administered CPT-loaded micelles demonstrated a significant reduction on tumor incidence and inflammation signs. The findings here reported indicate that CPT-loaded into chitosan-based micelles, by improving drug solubility, alongside its safety profile for normal tissues, may have a promising role CRC chemotherapy.

Salicylic acid directly binds to ribosomal protein S3 and suppresses CDK4 expression in colorectal cancer cells

Colorectal cancer is a significant cause of morbidity and represents a serious public health issue in many countries. The development of a breakthrough preventive method for colorectal cancer is urgently needed. Aspirin has recently been attracting attention as a cancer preventive drug, and its inhibitory effects on the development of various cancers have been reported in several large prospective studies. However, the underlying molecular mechanisms have not yet been elucidated in detail. In the present study, we attempted to identify the target proteins of aspirin using a chemical biology technique with salicylic acid, the main metabolite of aspirin. We generated salicylic acid-presenting FG beads and purified salicylic acid-binding proteins from human colorectal cancer HT-29 cells. The results obtained showed the potential of ribosomal protein S3 (RPS3) as one of the target proteins of salicylic acid. The depletion of RPS3 by siRNA reduced CDK4 expression and induced G1 phase arrest in human colorectal cancer cells. These results were consistent with the effects induced by the treatment with sodium salicylate, suggesting that salicylic acid negatively regulates the function of RPS3. Collectively, the present results show the potential of RPS3 as a novel target for salicylic acid in the protective effects of aspirin against colorectal cancer, thereby supporting RPS3 as a target molecule for cancer prevention.

Improve the cytotoxic effects of megavoltage radiation treatment by Fe3O4@Cus–PEG nanoparticles as a novel radiosensitizer in colorectal cancer cells

BackgroundTo enhance the performance of radiotherapy, emerging nanoparticles that can professionally enhance X-ray irradiation to destruct cancer cells are extremely necessary. Here, we examined the potential of PEG-coated magnetite copper sulfide hetero-nanoparticles (Fe3O4@Cus–PEG) as a radiosensitizer agent.MethodsFe3O4@Cus–PEG nanoparticles were synthesized and characterized. The toxicity of nanoparticles on HT-29 colorectal cancer cells was assessed by the MTT assay. The radio-sensitizing effects of Fe3O4@Cus–PEG nanoparticles on HT-29 cancer cells were investigated by the MTT and colony formation assays. Moreover, the underlying mechanisms for Fe3O4@Cus–PEG nanoparticles to improve the radiation sensitivity of cells were evaluated.ResultsThe results demonstrated that nanoparticles enhanced the effects of X-ray irradiation in a dose-dependent manner. The effects of combined treatments (nanoparticles and X-ray radiation) were strongly synergistic. The sensitizing enhancement ratio (SER) of nanoparticles was 2.02. Our in vitro assays demonstrated that the nitric oxide production, the intracellular hydrogen peroxide concentration, and the expression level of Bax and Caspase-3 genes significantly increased in the cells treated with the combination of nanoparticles and radiation. Whereas, the Glutathione peroxidase enzyme activity and the expression level of the Bcl-2 gene in the combined treatment significantly decreased compared to the radiation alone.ConclusionsOur study suggests that Fe3O4@Cus–PEG nanoparticles are the promising nano radio-sensitizing agents for the treatment of cancer cells to enhance the efficacy of radiation therapy through increasing the reactive oxygen species generation, nitric oxide production, and inducing apoptosis.Graphical

Benzimidazole-hydrazone derivatives: Synthesis, in vitro anticancer, antimicrobial, antioxidant activities, in silico DFT and ADMET studies

Based on the biologically active heterocycle compounds, a series of new benzimidazole-hydrazone derivatives (3a-3j) were synthesized, starting from 4-(6-chloro-1H-benzimidazol-2-yl) benzohydrazide. The synthesized compounds were characterized by 1H NMR, 13C NMR, and HRMS spectroscopic methods. The synthesized compounds were preliminarily evaluated for their in vitro antimicrobial, anticancer and antioxidant activity. The antimicrobial activity was checked against S. aureus ATCC 29213, E. coli ATCC 25922, and C. albicans ATCC 10231 by micro-dilution method. The findings exhibited that the compounds possessed moderate antimicrobial potential. The compounds were also checked for their in vitro anticancer activities against HT-29 (colorectal cancer cell line) using the MTT assay. It was observed that all the compounds 3a-3j showed weak antiproliferative activity against HT-29 cells. The compounds were also analyzed for their antioxidant capacity by Tas & Tos activity. The compound 3d showed a high anti-oxidative effect with 30.81 µmol H2O2 Equiv./L value. The lowest energy state of compound 3d was realized in DMSO medium by using the B3LYP method at 6–311G (d,p) level, the optimized geometry of it is about 0.50 and 17 kcal/ mol more stable than in other solvents and the gas phase, respectively. The lower ΔE=3.563 eV indicates the higher reactivity of compound 3d, this is compatible with biological experimental data and shows high antioxidant property of the compound. In silico ADMET studies of compound 3d were performed. Indexing of the X-ray powder diffraction pattern was performed for compound 3a.