HT-29 Colon Cancer Cells Research Articles

Survival of HT29 Cancer Cells Is Affected by IGF1R Inhibition via Modulation of Self-DNA-Triggered TLR9 Signaling and the Autophagy Response.

Purpose: In HT29 colon cancer cells, a close interplay between self-DNA-induced TLR9 signaling and autophagy response was found, with remarkable effects on cell survival and differentiation. IGF1R activation drives the development and malignant progression of colorectal cancer. IGF1R inhibition displays a controversial effect on autophagy. The interrelated roles of IGF1R inhibition and TLR9/autophagy signaling in HT29 cancer cells have not yet been clarified. In our study, we aimed to investigate the complex interplay of IGF1R inhibition and TLR9/autophagy signaling in HT29 cells. Methods: HT29 cells were incubated with tumor-originated self-DNA with or without inhibitors of IGF1R (picropodophyllin), autophagy (chloroquine), and TLR9 (ODN2088), respectively. Cell proliferation and metabolic activity measurements, direct cell counting, NanoString and Taqman gene expression analyses, immunocytochemistry, WES Simple Western blot, and transmission electron microscopy investigations were performed. Results: The concomitant use of tumor-derived self-DNA and IGF1R inhibitors displays anti-proliferative potential, which can be reversed by parallel TLR9 signaling inhibition. The distinct effects of picropodophyllin, ODN2088, and chloroquine per se or in combination on HT29 cell proliferation and autophagy suggest that either the IGF1R-associated or non-associated autophagy machinery is “Janus-faced” regarding its actions on cell proliferation. Autophagy, induced by different combinations of self-DNA and inhibitors is not sufficient to rescue HT29 cells from death but results in the survival of some CD133-positive stem-like HT29 cells. Conclusion: The creation of new types of combined IGF1R, autophagy, and/or TLR9 signaling inhibitors would play a significant role in the development of more personalized anti-tumor therapies for colorectal cancer.

Facile synthesis of ZnO-NPs from yellow creeping daisy (Sphagneticola trilobata L.) attenuates cell proliferation by inducing cellular level apoptosis against colon cancer

Cancer is considered as one of the relatively high mortality diseases to humankind and the search for newer strategies to combat the disease is a never-ending process. In view of the same the present study was designed to biosynthesize zinc oxide nanoparticles (ZnO-NPs) from the aqueous leaf extract (ALE) of medicinally important plant Sphagneticola trilobata L. for the first time and to evaluate its efficacy in inducing cancer against HT-29 cells apart from identifying their biocompatible potential. The as-prepared StZnO-NPs were characterized by different techniques that signified the properties of the nanoparticles, which included an absorption peak at 298 nm, bandgap energy of 3.43 eV with a size of ∼ 29.83 nm. The scanning electron microscopic images confirmed the particles were agglomerated and the energy dispersive spectroscopic analysis confirmed the particles were of 98.23% purity. The Fourier transform infrared spectroscopy revealed that the metabolites of the ALE act as reducing/ stabilizing agents during the synthesis process which was confirmed by the presence of absorbance peak between 400 cm−1 to 600 cm−1. The StZnO-NPs also offered potential antioxidant and genotoxic potential with an IC50 value of 0.7 mg mL−1. In addition, the cytotoxic ability of the StZnO-NPs against the HT-29 colon cancer cells and human erythrocytes revealed that the particles were cytotoxic towards HT-29 cells, while insignificant effect against the human erythrocytes. Further, a detailed investigation on the interaction with cells and their inherent toxicity may be enhanced through in vivo methods before their therapeutic usage as the StZnO-NPs evaluated during the study offered antioxidant, genotoxic and cytotoxic properties is biocompatible.

Inhibitory Effect of Lotus Leaf-Enriched Flavonoid Extract on the Growth of HT-29 Colon Cancer Cells through the Expression of PI3K-Related Molecules.

Objectives Lotus leaf is rich in flavonoids, and this study is aimed at examining the inhibitory effect of lotus leaf-enriched flavonoid extract (LLEFE) on HT-29 colon cancer cells through phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) expression regulation. Methods Lotus leaves were extracted by ethanol and purified using FL-3 macroporous resin to create the LLEFE. HT-29 colon cancer cells were tested using various methods: their proliferation was observed by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, their survival status was observed by fluorescence staining, their oxidative stress level was observed by biochemical kits, and their mRNA expression was determined by quantitative polymerase chain reaction (qPCR) assay. Additionally, the composition of the flavonoids in lotus leaf was determined by HPLC. Results The results showed that the proliferation of NCM460 normal human colon cells was not affected by 0–500 μg/mL LLEFE but the proliferation of HT-29 human colon cancer cells decreased. LLEFE increased the LDH level in an HT-29 colon cancer cell culture medium; also increased the superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) level in HT-29 cells; and decreased the malondialdehyde (MDA) level. Further experimental results showed that LLEFE upregulated the expression of SOD1, CAT, and GSH mRNA and downregulated the expression of PI3K, Akt, and mammalian target of rapamycin (mTOR) in HT-29 cells. The high-performance liquid chromatography (HPLC) results showed that kaempferin, hyperoside, astragaloside, phloridzin, and quercetin were the main chemical constituents of lotus leaf. Conclusion Lotus leaves contain functional flavonoids that inhibit the proliferation of HT-29 colon cancer cells and regulate the expression of PI3K/Akt through five important chemicals.

Effect of Uracil DNA Glycosylase Activity on the Efficacy of Thymidylate Synthase Inhibitor/HDAC Inhibitor Combination Therapies in Colon Cancer

Human uracil DNA glycosylase (UNG2) is responsible for removal of uracil bases from DNA and initiates base excision repair pathways. Accumulation of uracil or its fluorinated analogs in DNA is one of the killing mechanisms of thymidylate synthase (TS) inhibitors in cancer cells, and depletion of UNG2 often enhances the toxicity of these anticancer drugs. We used CRISPR to knockout UNG2 from HT29 colon cancer cells and confirmed the absence of protein by western blot and uracil excision assays. We tested the effect of UNG2 KO on the efficacy of multiple TS inhibitors (5‐fluorouracil, fluorodeoxyuridine, pemetrexed, and raltitrexed), and we determined that only fluorodeoxyuridine and raltitrexed were significantly more potent in UNG2 KO cells compared to wild‐type HT29 cells (fluorodeoxyuridine IC50: 2 mM (wt) vs. 3 nM (KO); raltitrexed IC50: 14 nM (wt) vs. 2 nM (KO)). Interestingly, UNG2 protein levels can also be depleted by the HDAC inhibitors SAHA and MS275, providing a pharmacologic strategy to reduce UNG2 activity in cells. Unexpectedly, the HDAC inhibitors synergized with 5‐fluorouracil, but not fluorodeoxyuridine, in both wild‐type and UNG2‐knockout cells. This suggested that HDAC inhibitors sensitized cells to 5‐fluorouracil through an UNG2‐independent mechanism. Moreover, cell death pathways activated by fluorodeoxyuridine and regulated by UNG2 activity are not sensitized by HDAC inhibitors. Our combined genetic and pharmacologic strategies targeting UNG2 activity in cells are defining cell death mechanisms for combination therapies of TS inhibitors and HDAC inhibitors. Future work will examine these drug combinations in additional cell lines to understand optimal therapeutic combinations and to further refine mechanisms of cell death.

Enhanced Growth Inhibition and Apoptosis Induction in Human Colon Carcinoma HT-29 Cells of Soluble Longan Polysaccharides with a Covalent Chemical Selenylation.

The selenylated polysaccharides chemically belong to the organic Se-conjugated macromolecules and have recently been attracting more and more attention due to their potential to promote body health or prevent cancers. Longan (Dimocarpus longan L.), as a subtropical fruit, contains soluble and non-digestible polysaccharides that are regarded with health care functions in the body. In this study, the longan polysaccharides (LP) were obtained via enzyme-assisted water extraction, and then chemically selenylated using a reaction system composed of HNO3–Na2SeO3 to yield two selenylated products, namely, SeLP1 and SeLP2, with Se contents of 1.46 and 4.79 g/kg, respectively. The anti-cancer effects of the three polysaccharide samples (LP, SeLP1, and SeLP2) were thus investigated using the human colon cancer HT-29 cells as the cell model. The results showed that SeLP1 and SeLP2 were more able than LP to inhibit cell growth, alter cell morphology, cause mitochondrial membrane potential loss, increase intracellular reactive oxygen and [Ca2+]i levels, and induce apoptosis via regulating the eight apoptosis-related genes and proteins including Bax, caspases-3/-8/-9, CHOP, cytochrome c, DR5, and Bcl-2. It was thereby proven that the selenylated polysaccharides could induce cell apoptosis via activating the death receptor, mitochondrial-dependent, and ER stress pathways. Collectively, both SeLP1 and SeLP2 showed higher activities than LP in HT-29 cells, while SeLP2 was consistently more active than SeLP1 in exerting these assessed anti-cancer effects on the cells. In conclusion, this chemical selenylation covalently introduced Se into the polysaccharide molecules and caused an enhancement in their anti-cancer functions in the cells, while higher selenylation extent was beneficial to the activity enhancement of the selenylated products.

Antitumor mechanisms of an exopolysaccharide from Lactobacillus fermentum on HT-29 cells and HT-29 tumor-bearing mice

We have obtained an exopolysaccharide (YL-11 EPS) produced by Lactobacillus fermentum YL-11 isolated from fermented milk and confirmed that it can effectively inhibit colon cancer HT-29 cells proliferation in vitro. The aim of this study is to study anti-colon cancer effect in vivo and its possible mechanisms. Animal assays indicated YL-11 EPS treatment significantly suppressed the growth of HT-29 tumor xenograft without exhibiting obvious negative effects on normal cells. Cell experiments demonstrated YL-11 EPS treatment up regulated the ratio of Bax/Bcl-2 and induced the decrease in mitochondrial membrane potential and improved the expression of cleaved caspases-3 and cleaved PARP proteins, and finally induced HT-29 cells apoptosis, suggesting the involvement of mitochondrial pathway. Moreover, YL-11 EPS can block the PI3K/AKT signaling pathway and arrest the cell cycle in G1-phase to exert its anti-colon cancer activity. Overall, YL-11 EPS can be explored as a potential nutraceutical to prevent colorectal cancer.

Cytotoxic benzylidene hydrazides of terephthalic acid and related compounds.

The present investigation involved the synthesis of a number of novel benzylidene hydrazides as candidate cytotoxic agents. The preparation of these compounds from terephthalic acid and isophthalic acid proceeded satisfactorily. However, the reaction of phthalic acid hydrazide with various aryl aldehydes was unsuccessful in general. Some of the unexpected products were identified. The shapes and also the distances between the centers of the aryl rings designated B and C of three representative compounds 1b, 2b and 3b were determined. The compounds designated 1a-e, 2a-e and 3b were screened against human HCT116 and HT29 colon cancer cells as well as human CRL1790 non-malignant colon cells which revealed the tumor-selective toxicity displayed by these compounds.

Cyclooxygenase-Inhibiting Platinum(IV) Prodrugs with Potent Anticancer Activity.

Platinum(IV) prodrugs of the [Pt(PL)(AL)(COXi)(OH)]2+ type scaffold (where PL is 1,10-phenanthroline or 5,6-dimethyl-1,10-phenanthroline, AL is 1S,2S-diaminocyclohexane, and COXi is a COX inhibitor, either indomethacin or aspirin) were synthesised and characterised, and their biological activity was explored. MTT assays showed that these complexes exhibit outstanding activity against a range of cancer cell lines, and nanomolar activities were observed. The most potent complex, 4, exhibited a GI50 of 3 nM in the Du145 prostate cancer cell line and was observed to display a 1614-fold increased activity against the HT29 colon cancer cell line relative to cisplatin. ICP-MS studies showed a linear correlation between increased cellular accumulation of the complexes and increased cytotoxicity, while an enzyme immunoassay showed that 1 and 2 inhibited COX-2 at 14 and 1.4 µM, respectively, which is comparable to the inhibition exhibited by indomethacin. These results suggest that while the cytotoxicity of prodrugs 1–4 was influenced by cellular uptake, it was not entirely dependent on either COX inhibition or lipophilicity.

Determination of anticancer potential of a novel pharmacologically active thiosemicarbazone derivative against colorectal cancer cell lines

Thiosemicarbazones have received noteworthy attention due to their numerous pharmacological activities. Various thiosemicarbazone derivatives have been reported to play a key role as potential chemotherapeutic agents for the management of cancer. Herein, we aimed to establish the anticancer efficacy of novel thiosemicarbazone derivative C4 against colon cancer in vitro. The MTT viability assay identified C4 as a promising anticancer compound in a panel of cancer cell lines with the most potent activity against colon cancer cells. Further, anticancer potential of C4 was evaluated against HT-29 and SW620 colon cancer cell lines considering the factors like cell adhesion and migration, oxidative stress, cell cycle arrest, and apoptosis. Our results showed that C4 significantly inhibited the migration and adhesion of colon cancer cells. C4 significantly increased the intracellular reactive oxygen species (ROS) and induced apoptotic cell death. Cell cycle analysis revealed that C4 interfered in the cell cycle distribution and arrested the cells at the G2/M phase of the cell cycle. Consistent with these results C4 also down-regulated the Bcl-XL and Bcl-2 and up-regulated the caspase-3 expression. These findings introduced C4 as the potential anticancer agent against colon cancer.

Lipid-Based Nanoparticle Formulation of Diallyl Trisulfide Chemosensitizes the Growth Inhibitory Activity of Doxorubicin in Colorectal Cancer Model: A Novel In Vitro, In Vivo and In Silico Analysis.

Garlic’s main bioactive organosulfur component, diallyl trisulfide (DATS), has been widely investigated in cancer models. However, DATS is not suitable for clinical use due to its low solubility. The current study seeks to improve DATS bioavailability and assess its chemopreventive and chemosensitizing properties in an AOM-induced colorectal cancer model. The polyethylene glycol coated Distearoylphosphatidylcholine/Cholesterol (DSPC/Chol) comprising DATS-loaded DATSL and doxorubicin (DOXO)-encapsulated DOXL liposomes was prepared and characterized. The changes in the sensitivity of DATS and DOXO by DATSL and DOXL were evaluated in RKO and HT-29 colon cancer cells. The synergistic effect of DATSL and DOXL was studied by cell proliferation assay in the combinations of IC10, IC25, and IC35 of DATSL with the IC10 of DOXL. AOM, DATSL, and DOXL were administered to different groups of mice for a period of 21 weeks. The data exhibited ~93% and ~46% entrapment efficiency of DATSL and DOXL, respectively. The size of sham liposomes was 110.5 nm, whereas DATSL and DOXL were 135.5 nm and 169 nm, respectively. DATSL and DOXL exhibited significant sensitivity in the cell proliferation experiment, lowering their IC50 doses by more than 8- and 14-fold, respectively. However, the DATSL IC10, IC25, and IC35 showed escalating chemosensitivity, and treated the cells in combination with DOXL IC10. Analysis of histopathological, cancer marker enzymes, and antioxidant enzymes revealed that the high dose of DATSL pretreatment and DOXL chemotherapy is highly effective in inhibiting AOM-induced colon cancer promotion. The combination of DATSL and DOXL indicated promise as a colorectal cancer treatment in this study. Intermolecular interactions of DATS and DOXO against numerous cancer targets by molecular docking indicated MMP-9 as the most favourable target for DATS exhibiting binding energy of −4.6 kcal/mol. So far, this is the first research to demonstrate the chemopreventive as well as chemosensitizing potential of DATSL in an animal model of colorectal cancer.

Potential Translational Thioflavin T Methodology as a Complement of Cell-Based Assays and after Drug Exposition

Protein aggregation is a common characteristic of several human diseases such as Alzheimer’s disease. Recent evidence has indicated that the aggregation of peptides such as p53 is also marked in cancer cells. The aim of this study was to correlate Thioflavin T (ThT) data with different cellular viability assays (Neutral Red and MTT) in SH-SY5Y neuroblastoma cells and HT-29 colon cancer cells treated with doxorubicin, a classical antineoplastic agent. We also studied the effects of the well-known peptide Aβ42 on the aggregation process in these cells. Our data suggest that both cancer cell lines are responsive to doxorubicin and formed aggregates, highlighting a relationship between ThT and cellular viability methodologies. We observed that lower values of cell viability corresponded with pronounced aggregation. Thus, these results indicated that the ThT methodology used in cells may complement the cell viability assays. In addition, this methodology may be of interest to evaluate the role of protein aggregation in other cancer cells.

Psoralidin, a natural compound from Psoralea corylifolia, induces oxidative damage mediated apoptosis in colon cancer cells.

Psoralidin (PSO) is a natural coumarin isolated from the seeds of Psoralea corylifolia Linn. Previous studies have reported that PSO exerts numerous pharmacological bioactivities including antitumor. The present study aimed to investigate its anticancer effect using colon cancer cells. Cultured HT-29 and HCT-116 colon cancer cells were treated with different concentrations of PSO, and the cell viability, the intracellular reactive oxygen species (ROS), the protein expression, and the apoptosis were determined by MTT assay, DCFH2 -DA fluorescence probe, Western blotting, and Annexin V/7-AAD staining, respectively. The activities of caspase 3/7 were determined by a commercial kit. Our study found that PSO effectively induces apoptotic cell death mediated by caspase 3/7 in HT-29 and HCT-116 colon cancer cells. PSO treatment rapidly boosts the ROS generation, which is responsible for the PSO-triggered DNA damage, mitochondria membrane potential decrease and caspase 3/7 activation, and c-Jun N-terminal kinase 1/2 activation. Collectively, these results showed that PSO triggered oxidative damage mediated apoptosis in colon cancer cells.

Anti‐angiogenic and anticancer activities of the nanoemulsions synthesized from Trachyspermum ammi L. tincture against human colon adenorectal carcinoma cells

In this study, an attempt has been made to synthesize nanoemulsions using Trachyspermum ammi tincture. The nanoemulsion specifications are characterized by TEM, DLS, and zeta potential. The anti-tumour and cell toxicity effects of the biosynthesized nanoemulsions are evaluated by chorioallantoic membrane (CAM) and MTT assays, respectively. For the CAM test, the length and number of blood vessels are evaluated around the gelatine sponge. According to DLS analysis, the nanoemulsions synthesized by the T. ammi tincture have an average hydrodynamic size of 34 nm. The cytotoxicity test shows little toxicity for the nanoemulsions against human foreskin fibroblast cells. On the other hand, the fabricated nanoemulsions show dose- and time-dependent toxicity against colon cancer cells (HT-29) and ovarian cancer cells (A2780) with an IC50 of 14 and 0.72 μg/ml, respectively. According to the CAM assay, the number and length of blood vessels and dose dependency significantly decrease after exposure to different concentrations of the nanoemulsions. In this study, a simple approach for the biosynthesis of nanoemulsions is explained. The nanoemulsions show dose-dependent cytotoxic effects against HT-29 colon cancer cells and inhibit the formation of blood vessels. The observed bioeffects indicate the potential of the fabricated nanoemulsions as effective chemotherapeutics for cancer treatment.

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...

Honeybee Venom Synergistically Enhances the Cytotoxic Effect of CNS Drugs in HT-29 Colon and MCF-7 Breast Cancer Cell Lines

5-fluorouracil (5-FU) and doxorubicin (DOX) are potent anti-tumour agents commonly used for colon and breast cancer therapy, respectively. However, their clinical application is limited by their side effects and the development of drug resistance. Honeybee venom is a complex mixture of substances that has been reported to be effective against different cancer cells. Its active compound is melittin, a positively charged amphipathic peptide that interacts with the phospholipids of the cell membrane, forming pores that enable the internalization of small molecules with cytotoxic activities,. and consequently, causing cell death. Some central nervous system (CNS) drugs have recently demonstrated great anti-cancer potential, both in vitro, in vivo and in clinical trials, being promising candidates for drug repurposing in oncology. The present work evaluated the anti-cancer efficacy of honeybee venom in combination with chemotherapeutic or CNS drugs in HT-29 colon and MCF-7 breast cancer cell lines. The chemical characterization of a Portuguese sample of honeybee venom was done by LC-DAD-ESI/MSn analysis. For single treatments, cells were incubated with increasing concentrations of bee venom. For combination treatments, increasing concentrations of bee venom were first combined with the half-maximal inhibitory concentration (IC50) of 5-FU and DOX, in HT-29 and MCF-7 cells, respectively. Cells were also treated with increasing concentrations of bee venom in combination with the IC50 value of four CNS drugs (fluphenazine, fluoxetine, sertraline and thioridazine). Cytotoxicity was evaluated by MTT and SRB assays. The combination index (CI) value was calculated using CompuSyn software, based on the Chou–Talalay method. Synergy scores of different reference models (HSA, Loewe, ZIP and Bliss) were also calculated using SynergyFinder. The results demonstrate that honeybee venom is active against HT-29 colon and MCF-7 breast cancer cells, having better anti-tumour activity in MCF-7 cells. It was found that bee venom combined with 5-FU and fluphenazine in HT-29 cells resulted in less cytotoxic effects compared to the co-treatment of fluoxetine, sertraline and thioridazine plus bee venom, which resulted in less than 15% of viable cells for the whole range of concentrations. The combination of MCF-7 cells with repurposed drugs plus honeybee venom resulted in better anti-cancer efficacies than with DOX, notably for lower concentrations. A combination of fluoxetine and thioridazine plus honeybee venom resulted in less than 40% of viable cells for all ranges of concentrations. These results support that the combination of honeybee venom with repurposed drugs and chemotherapeutic agents can help improve their anti-cancer activity, especially for lower concentrations, in both cell lines. Overall, the present study corroborates the enormous bioactive potential of honeybee venom for colon and breast cancer treatments, both alone and in combination with chemotherapy or repurposed drugs.

Synergic fabrication of multifunctional liposomes nanocomposites for improved radiofrequency ablation combination for liver metastasis cancer therapy

The field of biomedical research has recently been interested in nanoplatforms with various functionalities, such as cancer drug carriers and MRI and optical imaging, as well as thermal treatment, among other things. As a result of the present investigation, a unique multifunctional liposome (MFL) was established in this investigation. Using radiofrequency-induced imaging and drug release based on magnetic field impact, a dual drug delivery targeted with tumor multi-mechanism treatment was made more effective. The C60 (fullerene) surface was coated with iron nanocomposites to establish the proposed nanosystems, and PEGylation was used (Fe3O4-C60-PEG2000). For fullerene radiofrequency-triggered drug release, thermosensitive DPPC liposomes with folate-DSPE-PEG2000 enveloped the binary nanosystems and doxorubicin (DOX). The in vitro cytotoxicity of the nanocomposites was confirmed by the liver metastasis in HT-29 colon cancer cells using radiofrequency. The flow cytometry analysis confirmed the apoptosis cell death mechanism. The thermal treatment combined chemotherapeutic MFL nano framework transformed radiofrequency radiation from thermoresponsive liposomes, which was noticed both in vivo and in vitro. Due to their superior active tumor targeting and magnetic targeting characteristics, the MFL could also selectively destroy cancerous liver cells in highly co-localized targets.

Anti-cancer effects of pyrazole-platinum(II) complexes combined with anti-MUC1 monoclonal antibody versus monotherapy in DLD-1 and HT-29 colon cancer cells

The membrane-bound MUC1 mucin is overexpressed and aberrantly glycosylated in many epithelium origin cancers. One of the promising strategies in cancer therapy is combining monoclonal antibodies against cancer related antigens, like MUC1, with chemotherapeutics. In the study we evaluated the potency of cisplatin (cisPt), two pyrazole-platinum(II) complexes PtPz4, PtPz6, and anti-MUC1 mAb applied as monotherapy, as well as the chemotherapeutics administrated with antibody, towards apoptotic response and cancer-related carbohydrate antigens (TACAs) in DLD-1 and HT-29 colon cancer cells. To assess the impact of the tested compounds on the examined factors flow cytometry, RT-PCR, Western blotting and ELISA were utilized. The combined therapy was more potent than monotherapy towards Bcl-2, Bid, caspases and TACAs of both cell lines. Combined therapy applied in DLD-1 cells induced apoptosis, was more effective than monotherapy in relation to p53, Bcl-xL, Bax, and Bim. In HT-29 cells, anti-MUC1 administrated with the drugs was more potent than monotherapy towards Bad. The proposed anti-MUC1/cisPt and pyrazole-platinum(II) complexes PtPz4, PtPz6 combined therapy may be promising anti-colon cancer therapy.

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.