HT-29 Human Colon Cancer Cells Research Articles

Development and in vitro characterization of capecitabine loaded biopolymeric vehicle for the treatment of colon cancer

AbstractThe present study aims at developing and characterizing gum odina ‐ sodium alginate based microsphere as a carrier for capecitabine. Microspheres with varying concentration of polymers (gum odina and sodium alginate) were formulated using calcium chloride as a cross‐linker by ionotropic gelation technique. The formulated microspheres were optimized by entrapment efficiency, drug yield, particle size, swelling index, and in vitro drug release study. The optimized microsphere (F6) was characterized in terms of SEM, AFM, FTIR, XRD, degradation study, moisture content study, and antioxidant activity. The F6 was spherical in shape with a mean diameter of 568.33 ± 45.76 μm and drug entrapment efficiency of 45.91 ± 2.94%. In vitro dissolution study of optimized formulation exhibited negligible released in 0.1 N HCl (pH 1.2) and followed by 100% release in phosphate buffer (pH 7.4) within 24 h. In vitro cytotoxicity assay (MTT) of formulation F6 on HT29 human colon cancer cell line indicated inhibition of the proliferation of tumor cell over a longer period of time. The overall experiment indicated that capecitabine loaded natural polymers based formulated microsphere could be a promising approach for the prevention of colon cancer.

Characterization of Theabrownins Prepared From Tea Polyphenols by Enzymatic and Chemical Oxidation and Their Inhibitory Effect on Colon Cancer Cells.

Theabrownins (TBs) are prepared from dark tea and contain a large number of complex heterogeneous components, such as carbohydrates, proteins, and flavonoids, which are difficult to remove. In addition, some toxic and harmful extraction solvents are used to purify TBs. These obstacles hinder the utilization and industrialization of TBs. In this study, tea polyphenols were used as substrates and polyphenol oxidase and sodium bicarbonate (NaHCO3) were used successively to prepare theabrownins (TBs-E). The UV-visible characteristic absorption peaks of the TBs-E were located at 203 and 270 nm and Fourier-transform IR analysis showed that they were polymerized phenolic substances containing the hydroxy and carboxyl groups. The TBs-E aqueous solution was negatively charged and the absolute values of the zeta potential increased with increasing pH. A storage experiment showed that TBs-E were more stable at pH 7.0 and in low-temperature environments around 25°C. HT-29 human colon cancer cells were used to evaluate the biological activity of TBs-E through 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di- phenytetrazoliumromide (MTT), H&E staining, propidium iodide immunofluorescent staining, flow cytometry, and real-time PCR assays. The TBs-E significantly inhibited cell growth and caused late apoptosis, particularly at the dose of 500 μg/ml. The TBs-E markedly reduced the expression of antioxidant enzyme genes and increased the generation of reactive oxygen species to break the redox balance, which may have led to cell damage and death. These results will promote research and industrialization of TBs.

Examination of the impact molecular charge has on NTSR1-targeted agents incorporated with cysteine protease inhibitors

Our laboratory has previously reported a strategy of employing cysteine cathepsin (CC) inhibitors as adduct forming, trapping agents to extend the tumor residence time of neurotensin receptor subtype 1 (NTSR1)-targeted radiopharmaceuticals. As a follow-up, we herein report a small library of CC trapping agent (CCTA)-incorporated, NTSR1-targeted conjugates with structural modifications that reduce the number of charged functional groups for both the CCTA and the peptide targeting sequence. These modifications were pursued to reduce the renal uptake and increase the translational potential of the CCTA-incorporated, NTSR1-targeted agents as radiotherapeutics. The biological performance of these constructs was examined using a battery of in vitro and in vivo studies employing the NTSR1-positive HT-29 human colon cancer cell line as our model. In vitro studies confirmed the ability of these constructs to target the NTSR1 and efficiently form intracellular adducts with cysteine proteases. Biodistribution studies using an HT-29 xenograft mouse model revealed that truncation (removal of Lys6-Pro7) of the NTSR1-targeted peptide (177Lu-NE2a) had the greatest (3.7-fold) effect at lowering renal recognition/uptake relative to our previously reported construct. Other charge-reducing modifications to the CCTA resulted in unexpected increases in renal uptake. All of the constructs demonstrated similar levels of in vivo NTSR1-positive tumor targeting with the highest tumor residualization resulting from the construct containing the zwitterionic CCTA (177Lu-NE2a). In vivo adduct formation of the conjugates was confirmed using autoradiographic SDS-PAGE analysis.

TMT-Based Quantitative Proteomic Analysis Identified Proteins and Signaling Pathways Involved in the Response to Xanthatin Treatment in Human HT-29 Colon Cancer Cells.

Xanthatin is a plant-derived bioactive sesquiterpene lactone from the Xanthium strumarium L., and it has been used as a traditional Chinese medicine. Recently, many studies have reported that xanthatin has anticancer activity. However, a comprehensive understanding of the mechanism underlying the antitumor effects of xanthatin is still lacking. To systematically and comprehensively identify the underlying mechanisms of xanthatin on cancer cells, quantitative proteomic techniques were performed. Xanthatin induced HT-29 colon cancer cells death was detected by lactate dehydrogenase (LDH) release cell death assay. Differentially abundant proteins in two groups (xanthatin treatment groups and control groups) of human HT-29 colon cancer cells were identified using tandem mass tag (TMT) quantitative proteomic techniques. All the significant differentially abundant proteins were generally characterized by performing hierarchical clustering, Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. We chose Western blot analysis to validate the candidate proteins in the proteomics results. A total of 5637 proteins were identified, of which 397 significantly differentially abundant proteins in the groups were quantified. Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses, we found that p53-related signaling played an important role in xanthatin-treated HT-29 colon cancer cells. p53- upregulated modulator of apoptosis (Puma), Sestrin-2 and p14ARF, which were selected from among p53-related signaling proteins, were further validated, and the results were consistent with the tandem mass tag quantitative proteomic results. We first investigated the molecular mechanism underlying the effects of xanthatin treatment on HT-29 colon cancer cells using tandem mass tag quantitative proteomic methods and provided a global comprehensive understanding of the antitumor effects of xanthatin. However, it is necessary to further confirm the function of the differentially abundant proteins and the potentially associated signaling pathways.

In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies

BackgroundColorectal cancer (CRC) is one of the most prevalent and deadly tumors worldwide. The majority of CRC is resistant to anti-programmed cell death-1 (PD-1)-based cancer immunotherapy, with approximately 15% with...

Origanum majorana harvested from Al-Soda, Saudi Arabia promotes mitotic arrest and apoptosis in colon cancer cells

Colorectal cancer is reported as the third major incentive of cancer doom. The present work is meant to examine the anticancer potential of Origanum majorana leaf acetone extract (OMAE) to fight HT-29 human colon cancer cells. Biomolecules in OMAE were examined using Fourier Transform Infrared (FT-IR) spectroscopy. Reactive oxygen species (ROS) in OMAE was determined using an immunosobant assay. The cytotoxic effect of OMAE was tested by MTT assay. p53 gene expression level of OMAE-tread cells was measured using quantitative real-time PCR (qPCR). Apoptotic and cell cycle arrest effects of OMAE on HT-29 were analyzed by flow cytometry. Results revealed the presence of many functional groups and considerable amount of ROS in the extract. The extract could raise p53 expression level five folds over control. OMAE arrested the HT-29 at G2/M phase. OMAE has an apoptotic effect rather than necrotic effects Our discoveries give solid proof that O. majorana acetone extract has a capacity to stop colon cancer activity, at least, through the enlistment of cell division arrest as well as apoptosis. These findings can suggest the use of OMAE as a natural therapeutic candidate against the colon cancer.

Chemical investigation and screening of anti-cancer potential of Syzygium aromaticum L. bud (clove) essential oil nanoemulsion.

This study was done to improve the medicinal properties of Syzygium Aromaticum L by processing S. Aromaticum L. bud essential oil (SABE) to the Nanoemulsion drug delivery system (SABE-NE) and investigating its anti-tumor and apoptotic impacts against the human HT-29 colon cancer cells. Applying the ultra-sonication method and characterization by DLS and FESEM analysis facilitates the nanoemulsification procedure. Human cancer (HT-29) and normal (HFF) cell lines were then evaluated based on the SABE-NE apoptotic and cytotoxic effects. In an in vitro section, flow cytometry method, Cas3 gene profile, AO/PI cell staining, and MTT assays are used to analyze the apoptotic and cytotoxic activities. In further analysis, liver lipid peroxidation and antioxidant genes expression (SOD, CAT, and GPx) investigate alterations in mice organs. As a result, produced 131.2nm SABE-NE induces apoptosis response and cellular death (Cas3 up-regulation and enhanced SubG1 peaks). Subsequently, the HT-29 cells' viability can reduce significantly, while HFF cells indicate confined cytotoxic impacts. Moreover, in vivo test results on mice livers demonstrate the cytoprotective properties of SABE-NE (reduced lipid peroxidation and increased antioxidant enzymes gene expression and nondetectable cytotoxic impacts). We produced a novel nanoemulsion drug delivery system called SABE-NE, a cell-specific apoptotic inducer. We thus can be utilized as an efficient anti-cancer compound for human colon cancer treatment. However, further supplementary studies are required to verify and approve its cell-specific anti-tumor activity.

Green synthesis and biological characterization of cerium oxide nanoemulsion against human HT-29 colon cancer cell line

ABSTRACT In this research, the cerium oxide nanoparticles (CeO2-NPs) were synthesized using Spirulina platensis microalgae. CeO2-NPs were nano-encapsulated based on ultrasonic emulsification method. Morphology, size, and stability of cerium oxide nanoemulsion (CeO2-NE) were verified by TEM, SEM, DLS, and zeta-potential. Antioxidant, antimicrobial against Escherichia coli and Staphylococcus aureus, and cytotoxic (on cancer cell line HT-29 and normal cell HFF) were performed comparatively between CeO2-NE and CeO2-NPs. Apoptotic and antioxidant related genes expression were determined in HT-29 treated cells with the CeO2-NE by Q-PCR. The CeO2-NE showed a much greater effect on anticancer activity, growth inhibition of two bacterial strains, antioxidant capacity, and reduction of ferric ions. Overexpression of caspase-3, caspase-8 and, caspase-9 of CeO2-NE confirmed apoptosis. Upregulation of superoxide dismutase attributed to the cellular redox potential of CeO2-NE in HT-29 cells. In conclusion, the CeO2-NE provides more efficient biological applications that could turn it into a promising factor for cancer treatment.

Mechanism of Pterostilbene-Induced Cell Death in HT-29 Colon Cancer Cells.

Pterostilbene is a dietary phytochemical that has been found to possess several biological activities, such as antioxidant and anti-inflammatory. Recent studies have shown that it exhibits the hallmark characteristics of an anticancer agent. The aim of the study was to investigate the anticancer activity of pterostilbene against HT-29 human colon cancer cells, focusing on its influence on cell growth, differentiation, and the ability of this stilbene to induce cell death. To clarify the mechanism of pterostilbene activity against colon cancer cells, changes in the expression of several genes and proteins that are directly related to cell proliferation, signal transduction pathways, apoptosis, and autophagy were also evaluated. Cell growth and proliferation of cells exposed to pterostilbene (5–100 µM) were determined by SRB and BRDU assays. Flow cytometric analyses were used for cell cycle progression. Further molecular investigations were performed using quantitative real-time RT-PCR. The expression of the signaling proteins studied was determined by the ELISA method. The results revealed that pterostilbene inhibited proliferation and induced the death of HT-29 colon cancer cells. Pterostilbene, depending on concentration, caused inhibition of proliferation, G1 cell arrest, and/or triggered apoptosis in HT-29 cells. These effects were mediated by the down-regulation of the STAT3 and AKT kinase pathways. It may be concluded that pterostilbene could be considered as a potential therapeutic option in the treatment of colon cancer in the future.

Effects of Sphingosine 1-Phosphate/Sphingosine-1-Phosphate Receptor on Pro-Angiogenesis in HT-29 Human Colon Cancer Cells

To investigate the effects and mechanism of sphingosine-1-phosphate/sphingosine-1-phosphate receptor on pro-angiogenesis in human colon cancer cells is the main objective. The effects of sphingosine-1-phosphate on the pro-angiogenesis in human colon cancer cells HT-29 and SW480 were assessed by tube formation assay. Quantitative real-time polymerase chain reaction was used to detect the expression of interleukin-8, interleukin-6 and vascular endothelial growth factor in HT29 and SW480 cells after sphingosine-1-phosphate treatment. Small interfering ribonucleic acid was designed to silence the expression of sphingosine-1- phosphate receptor 1, sphingosine-1-phosphate receptor 2 and sphingosine-1-phosphate receptor 3 in HT-29 and SW480 cells. Western blot and quantitative real-time polymerase chain reaction were used to assess the down-regulation efficiency of sphingosine-1-phosphate receptor in HT-29 and SW480 cells. Later, the effects of sphingosine-1-phosphate receptor were detected by quantitative real-time polymerase chain reaction. Tube formation assay showed that the number of formed tubes in human umbilical vein endothelial cell-fused cells (EA.hy926) resuspended in the culture supernatant from HT-29 and SW480 cells treated with sphingosine-1-phosphate was significantly more than that of the control group (t=3.667 and 4.881, p=0.021 and 0.013), indicating that sphingosine-1-phosphate promoted the pro-angiogenic ability of colon cancer cells. Moreover, the messenger ribonucleic acid expression of interleukin-8, interleukin-6 and vascular endothelial growth factor were significantly increased after sphingosine-1-phosphate treatment compared to the control group (p<0.05) where sphingosine-1-phosphate receptor 1 gene silence could significantly decrease the messenger ribonucleic acid expression in HT-29 and SW480 cells (p<0.05), while sphingosine-1-phosphate receptor 2 and sphingosine-1-phosphate receptor 3 gene silence did not lead to significant messenger ribonucleic acid changes. Sphingosine-1-phosphate up-regulated the expression of interleukin-8, interleukin-6 and vascular endothelial growth factor in human colon cancer cells through sphingosine-1-phosphate receptor 1 and thereby enhancing the proangiogenic effect of colon cancer cells. The sphingosine-1-phosphate/sphingosine-1-phosphate receptor pathway is a promising novel therapeutic target for inhibiting colon cancer growth.

Genomic and Phenotypic Characteristics in Geographically Separated Clinical Campylobacter jejuni ST353CC Isolates.

Campylobacter jejuni fecal isolates of eight international travelers, 5 of which had traveled to Ecuador and 3 to Bangladesh, were characterized, and the possible relationship between bacterial traits and clinical symptoms was further analyzed. All eight isolates belonged to the same Multi-Locus Sequence Type clonal complex (ST353CC). The three isolates from Bangladesh were all of the same sequence type (ST-9438), and when compared to isolates of various other sequence types, they had a larger quantity of unique genetic content, higher expression levels of some putative virulence genes involved in adhesion and invasion (flpA, ciaB and iamA), and showed higher adhesion levels to human HT-29 colon cancer cells in an in vitro infection model. However, in contrast to the seemingly higher pathogenic potential of these bacterial isolates, travelers infected with the ST-9438 isolates had no or only very mild symptoms, whereas the other individuals, whose bacterial isolates seemed to have less pathogenic potential, generally reported severe symptoms. When studying the 16S rRNA gene-based fecal microbiota in samples collected prior to travel, there was an individual variation in the relative abundance of the three major bacterial phyla Actinobacteria, Bacteroidetes and Firmicutes, but there were no associations between composition and diversity of microbiota and development of severe symptoms from the infection. It remains to be confirmed by larger studies whether an individual’s characteristics such as gut microbiota, might be related to the severity of symptoms in Campylobacter infections.

Antioxidant and Anti-Inflammatory Activity of Coffee Brew Evaluated after Simulated Gastrointestinal Digestion.

Coffee contains human health-related molecules, namely polyphenols that possess a wide range of pharmacological functions, and their intake is associated with reduced colon cancer risk. This study aimed to assess the changes in the anti-inflammatory and antioxidant activity of coffee after simulated gastrointestinal digestion. The evaluation of intracellular reactive oxygen species (ROS) levels in the HT-29 human colon cancer cell line and three in vitro spectrophotometric assays were performed to determine the antioxidant activity of the samples. Characterization of coffee composition was also assessed through a Q-Orbitrap high-resolution mass spectrometry analysis. The results highlighted that the levels of polyphenols in the digested coffee brews were higher than those of the non-digested ones. All assayed samples decreased the levels of intracellular ROS when compared to untreated cells, while digested coffee samples exhibited higher antioxidant capacity and total phenolic content than not-digested coffee samples. Digested coffee samples showed a higher reduction in interleukin-6 levels than the not-digested samples in lipopolysaccharide-stimulated HT-29 cells treated for 48 h and fewer cytotoxic effects in the MTT assay. Overall, our findings suggest that coffee may exert antioxidant and anti-inflammatory properties, and the digestion process may be able to release compounds with higher bioactivity.

Real-Time Impedance Monitoring of Alkaline Phosphatase (ALP) Release by Microelectrode Arrays

Alkaline phosphatase (ALP) is a reporter enzyme widely used in point-of-care applications. Real-time monitoring of ALP accelerates understanding of emerging diseases and of cancer progression. This can be achieved through biosensor-based strategies. This paper outlines an approach that facilitates the real-time monitoring of ALP release from the differentiation of cultured human colon cancer cells (Ht-29). Electric cell-substrate impedance sensing was used to generate changes in Ht-29 cells during ALP release and the data were compared using amperometry. The findings indicate a correlation between cell response and shift in impedance magnitude and current. Relevant results had similar attitude during cell monitoring, which influenced cell morphology and cell viability. Our analysis is a clear advance on the current methods such as enzyme-linked immunosorbent assay. The developed method can contribute to the development of microfluidic testing that would facilitate work on small-scale techniques.

Regulation of Butyrate-Induced Resistance through AMPK Signaling Pathway in Human Colon Cancer Cells.

Butyrates inhibit cell growth in colon cancer cells by inhibiting histone deacetylases. However, chronic exposure to butyrates induces butyrate resistance in colon cancer cells. The mechanism underlying the acquisition of resistance is not yet fully understood. Here, butyrate-resistant (BR) colon cancer cells were developed in HCT116, HT29, and SW480 human colon cancer cells and were confirmed by the increase in the inhibitory concentrations of cell growth by 50% (IC50) compared to their respective parental (PT) cells. Chronic exposure to butyrate induced autophagy via higher expression of Beclin-1 and LC3B-II. The AMP-activated protein kinase (AMPK) was downregulated along with the activation of Akt and mammalian target of rapamycin (mTOR) and decrease in acetyl-CoA carboxylase (ACC) in BR colon cancer cells compared to those in their respective PT cells. Activation of AMPK by AICAR treatment in BR colon cancer cells suppressed cell proliferation by inhibiting Akt and mTOR and activating ACC. Taken together, chronic exposure to butyrate increased butyrate resistance in human colon cancer by inducing protective autophagy through the downregulation of AMPK/ACC and activation of Akt/mTOR signaling. Activation of AMPK restored sensitivity to butyrate by the inhibition of Akt/mTOR, suggesting that AMPK could be a therapeutic target for BR colon cancers.

The new andrographolide derivative AGS-30 induces apoptosis in human colon cancer cells by activating a ROS-dependent JNK signalling pathway

Background: The anti-cancer activity of andrographolide (Andro) has been extensively demonstrated in recent years. It is supposed that modifying the chemical structure of Andro can improve its efficacy and reduce its toxicity. Purpose: In this study, the anti-cancer effect of a 14β-(2′-chlorophenoxy) derivative of andrographolide known as AGS-30 was investigated, and its underlying mechanisms were also explored. Study Design/Methods: Different cancer cells were used to evaluate and compare the in vitro anti-cancer effects of Andro and AGS-30. Human colon cancer cells HT-29 and HCT-116 were used to study the underlying anti-cancer mechanisms of AGS-30. HT-29 cells xenografted in nude mouse model was used to compare the in vivo anti-tumour efficacies of Andro and AGS-30. Result:In vitro studies showed that AGS-30 possessed an anti-cancer effect by inhibiting the viability, colony formation and migration of cancer cells. It significantly induced the generation of reactive oxygen species (ROS), caused the loss of mitochondrial membrane potential and triggered the apoptosis in colon cancer cells. These effects of AGS-30 were more potent than those of Andro. In addition, the expression levels of proteins associated with apoptosis, including phospho-JNK1/2 as well as cleaved caspase 9, caspase 3, and poly(ADP ribose) polymerase, were elevated in AGS-30-treated colon cancer cells. Moreover, these elevated levels of the proteins were inhibited by the antioxidant N-acetylcysteine and the JNK inhibitor SP600125, suggesting the involvement of ROS/JNK-dependent mechanisms in AGS-30-induced apoptosis. The in vitro anti-cancer effect could be reproduced in an HT-29 colon cancer cell xenografted nude mouse model. Conclusion: The anti-cancer effect of AGS-30 is stronger than that of Andro. AGS-30 induces apoptosis of colon cancer cells through ROS/JNK-dependent pathway. Our findings may provide insights for the future development of derivatives of Andro as novel chemotherapeutic agents.

A bis indole analog molecule fluorescent probe for living cell staining

In this study, the fluorescent probe property of a bis indole compound (5,14-dimethyl-5,6,7,8,9,14-hexahydroindolo [2 ', 3′: 3,4] cycloocta [1,2-b] indole), a Caulerpin derivative, which is a member of the indole family, was investigated. For this purpose, firstly, the fluorescence character of the molecule was investigated by absorption and fluorescence spectroscopy techniques in both solvent and surfactant environments. Afterwards, the cytotoxicity of the molecule was tested on the human colon cancer HT-29 cells and breast cancer MCF-7 cells as well as mouse fibroblast 3T3-L1 cells. After determining that the molecule has no cytotoxic effect against all the tested cell lines by 100 µM, the cell staining feature of the probe was examined. The obtained data showed us that the molecule, whose confocal microscopy images were taken at 360 nm excitation wavelength, stained the cell cytoplasm. In addition, optical absorption spectra, oscillator strength (f), transition configuration and transition characteristics of the Ars-In in different solvents were investigated at the theoretical level using Time Dependent-Density Functional Theory (TD-DFT). In conclusion, these results confirm that this indole derivative molecule could be evaluated as an effective fluorescence probe for biological systems.

Biomedical potential of silver nanoparticles capped with active ingredients of Hypnea valentiae, red algae species

In this present study, marine red algae Hypnea valentiae capped silver nanoparticles (Hv-AgNPs) have been prepared through the green method and characterized by various analytical tools. The prepared Hv-AgNPs were confirmed by Ultraviolet-visible (UV) spectroscopy at 430 nm. The X-ray diffraction (XRD) analysis affirmed the face-centered cubic crystalline structure of Hv-AgNPs. Transmission electron microscope (TEM) revealed the Hv-AgNPs shape as spherical with an average size of 10–45 nm. Fourier Transform Infrared (FR-IR) analysis depicted the presence of various biomolecules such as carboxyl, phenolic, and amine groups, which acted as reducing and capping agents of biosynthesized silver nanoparticles. The Hv-AgNPs had significant antibacterial activity against four bacterial pathogens. The 2,2’-Diphenyl-1-picrylhydrazy (DPPH) assay revealed the strong free radical scavenging ability of Hv-AgNPs. The Hv-AgNPs exhibited excellent anti-cancer activity against HT-29 human colon cancer (IC50–24.6 μg/ml) and A549 lung cancer cell lines (IC50–5.917 µg/ml) by MTT assay. Furthermore, the investigations demonstrated that green synthesized silver nanoparticles possess high anti-bacterial, anti-oxidant and anti-cancer activities.

Evaluation of Radiosensitive Effect of Tolmetin in Radiotherapy on Human Colonic Carcinoma Cell Line HT-29

Background: Radiotherapy is one of the cancer treatment methods. Although radioresistance and normal tissue toxicity limit the radiation therapy in certain anatomical locations, using some substances can be useful to increase radiosensitivity on cancer cells without cytotoxicity effect on normal cells. Objective: This study aimed to evaluate the radiosensitizing effect of tolmetin in radiotherapy treatment on human colon cancer cell line HT-29. Methods In this study, human colon cancer cells HT-29 in different groups were irradiated with 4 Gy x-ray, and tolmetin was administered in different concentrations (75, 100, and 150 μM). Then, the groups were compared with each other and with the control group by Micronucleus Assay (MN) and Nuclear Division Index (NDI). NDI investigated the cytotoxicity, and MN indicated the genotoxicity. Results: In the group receiving radiation, micronuclei increased significantly compared to the control group. In the group receiving tolmetin with a concentration of 75 and 100 μM, the number of micronuclei also increased compared to the control group. In all groups treated with tolmetin that also received radiation, a significant increase in micronuclei was observed, which was more noticeable at concentrations of 100 and 150 μM. At the same time, tolmetin at the studied concentrations did not change the NDI index. Conclusion: The present study demonstrates that tolmetin has a radiosensitizing effect on HT-29 colon cancer cells, which depends on the tolmetin concentration. In addition, tolmetin has no cytotoxic effect on this cell line.

Synergistic Anti-proliferative Effects of Lenalidomide and Dexamethasone on the HT-29 Cell Line Through Apoptotic Genes

Background: Colorectal cancer (CRC) is the third most common cancer among men and the second most common type of cancer among women worldwide. The resistance of tumor cells to apoptosis is caused by changes in the expression of anti-apoptotic or pro-apoptotic proteins. Histone deacetylase inhibitors (HDACi) are known to cause changes in gene expression. Objectives: The present study aimed at investigating the anti-proliferative effects of lenalidomide (LEN) as HDACi and dexamethasone (DEX) on the human colon cancer HT-29 cell line. Methods: The HT-29 cell line was treated with various concentrations of LEN and DEX individually and in combination for 24, 48, and 72 hours. Cytotoxicity was evaluated by MTT assay. The half-maximal inhibitory concentration (IC50) was measured, and quantitative real-time polymerase chain reaction (qRT-PCR) was also performed to examine the expression of Bcl2, Bax, Fas, and FasL genes. Results: The combination of LEN (1000 µM) with DEX (100 µM) showed potent synergistic anti-proliferative activities in a time- and dose-dependent manner. The combination of these drugs induced cell death by affecting the extrinsic and intrinsic apoptotic gene expression profiles. Conclusions: The combination of LEN with DEX can be proposed as a new therapeutic approach for CRC.

Biocompatible Eu doped mesoporous calcium silicate nanospheres for pH-responsive drug release

Calcium silicate is a kind of inorganic biomaterial containing Si, Ca, O elements, they have been widely investigated and applied in a variety of medical applications in the past four decades. Herein, Europium (Eu) doped mesoporous calcium silicate nanoparticles (Eu-MCS) with sizes ranging from 60 nm to 110 nm were prepared via a simple hydrothermal synthesis method. The morphology, structure, texture and optical property were characterized by SEM, TEM, XRD, N2 adsorption/desorption and PL spectra, respectively. The prepared material emits strong red luminescence at 613 nm upon UV irradiation and is cytocompatible at a wide range of concentrations, exibiting promising application in bioimaging. The Eu-MCS has a high loading capacity of 356.67 μg/mg for the anticancer drug DOX, and the drug loaded material DOX@Eu-MCS showed pH-controlled drug release behaviour. Moreover, both of the biocompatibility tests on normal human cells HEK293 and human colon cancer cells HT29 indicate a low cytotoxicity of Eu-MCS. The cell cytotoxity assays of the DOX loaded nanomaterial (DOX@Eu-MCS) on Hela cancer cells prove a high cancer cell mortality. Therefore, the as-prepared red emissive nanocarrier Eu-MCS has great potential to be used as an integrated platform for cancer diagnosis and therapy.