HCT116 Human Colon Cancer Cells Research Articles

Synthesis, characterization, and biological activity of 1,3-disubstitued benzimidazolium salt and its Ag-NHC complex

In this study, a 1,3-dioxane functionalized benzimidazole salt and its Ag-complex were synthe-sized. The prepared compounds were structurally verified by several spectroscopic techniques including 1H NMR, 13C NMR, FT-IR, LC-MS, and C, H, N analysis. Compounds were evaluated for their in vitro antioxidant activity. The salts and their Ag-NHC complexes were further evaluated for their in vitro anti-cancer activities against HCT-116 human colon cancer cells. The results showed that complex 2 exhibited high activity (4.1 times) against the cancer cell lines studied when compared to the reference drug cispla-tin. Stability studies demonstrated that these compounds are stable in aqueous and organic solutions.

Ellagic acid inhibits human colon cancer HCT-116 cells by regulating long noncoding RNAs.

The natural phenolic compound ellagic acid exerts anti-cancer effects, including activity against colorectal cancer (CRC). Previously, we reported that ellagic acid can inhibit the proliferation of CRC, and can induce cell cycle arrest and apoptosis. This study investigated ellagic acid-mediated anticancer effects using the human colon cancer HCT-116 cell line. After 72 h of ellagic acid treatment, a total of 206 long noncoding RNAs (lncRNAs) with differential expression greater than 1.5-fold were identified (115 down-regulated and 91 up-regulated). Furthermore, the co-expression network analysis of differentially expressed lncRNA and mRNA showed that differential expressed lncRNA might be the target of ellagic acid activity in inhibiting CRC.

Combining gamma-tocopherol and aspirin synergistically suppresses colitis-associated colon tumorigenesis and modulates the gut microbiota in mice, and inhibits the growth of human colon cancer cells

Despite being shown to be effective for chemoprevention of colorectal cancer, aspirin has limitations including adverse effects and inability to block colitis-associated colon cancer (CAC). γ-Tocopherol (γT), a vitamin E form, has been reported to mitigate experimental colitis and CAC, prolong the anti-inflammatory activity of aspirin and alleviate aspirin-induced adverse effect. We therefore hypothesize that combining γT and aspirin is better than either compound singly for suppressing CAC. This hypothesis was tested in the murine azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model and with human HCT116 colon cancer cells. Compared to the control, combining aspirin (250 ppm) and γT (500 ppm) but not either compound alone significantly reduced AOM/DSS-induced tumor area and multiplicity of large-size tumors by 60% and 50%, respectively. Meanwhile, γT mitigated aspirin-promoted inflammation and stomach lesions in mice. Moreover, the combination appeared to cause favorable changes of gut microbiota compared to the control and synergistically suppressed the growth of HCT116 cells. Our study demonstrates that combining aspirin and γT improves anticancer effects and counteracts side effects compared to aspirin and may therefore be a novel combinatory chemopreventive agent against CAC.

Resveratrol downregulates ENaCs through the activation of AMPK in human colon cancer cells

Epithelial sodium channels (ENaCs) are critically engaged in a number of hallmarks of cancer progression, including proliferation, migration, invasion and apoptosis. Thus, the inhibition of ENaCs possesses therapeutic potential in cancer. Resveratrol, a natural polyphenol with anti-carcinogenic activity, is a potent activator of 5′ AMP-activated protein kinase (AMPK) which reduces the abundance of ENaCs in the cell membrane by causing the internalization of the β subunit. However, the effect of resveratrol on ENaCs in cancer cells is unknown. Therefore, in this study, we aimed to investigate the effects of resveratrol on ENaCs in human colon cancer cells HCT116 and HT29. The influences of resveratrol either alone or together with AMPK inhibitor compound C (CC), and ENaC inhibitor amiloride on cell viability were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression levels of phospho-AMPK Thr172 and βENaC in cells were determined by immunofluorescence staining, and the expression of apoptotic markers Caspase-3 and Caspase-9 were analyzed by qRT-PCR. Resveratrol was found to activate AMPK in a dose-dependent manner. Both AMPK activation by resveratrol and ENaC inhibition by amiloride decreased cell viability and increased apoptosis significantly. AMPK activation also reduced βENaC expression in cells. Our results suggest that ENaC inhibition through AMPK activation might be a potential mechanism underlying the anti-cancer effects of resveratrol.

Appraisal of the Possible Role of PPARγ Upregulation by CLA of Probiotic Pediococcus pentosaceus GS4 in Colon Cancer Mitigation.

The prevalence of colon cancer (CC) is increasing at the endemic scale, which is accompanied by subsequent morbidity and mortality. Although there have been noteworthy achievements in the therapeutic strategies in recent years, the treatment of patients with CC remains a formidable task. The current study focused on to study role of biohydrogenation-derived conjugated linoleic acid (CLA) of probiotic Pediococcus pentosaceus GS4 (CLAGS4) against CC, which induced peroxisome proliferator-activated receptor gamma (PPARγ) expression in human CC HCT-116 cells. Pre-treatment with PPARγ antagonist bisphenol A diglycidyl ether has significantly reduced the inhibitory efficacy of enhanced cell viability of HCT-116 cells, suggesting the PPARγ-dependent cell death. The cancer cells treated with CLA/CLAGS4 demonstrated the reduced level of Prostaglandin E2 PGE2 in association with reduced COX-2 and 5-LOX expressions. Moreover, these consequences were found to be associated with PPARγ-dependent. Furthermore, delineation of mitochondrial dependent apoptosis with the help of molecular docking LigPlot analysis showed that CLA can bind with hexokinase-II (hHK-II) (highly expressed in cancer cells) and that this association underlies voltage dependent anionic channel to open, thereby causing mitochondrial membrane depolarization, a condition that initiates intrinsic apoptotic events. Apoptosis was further confirmed by annexin V staining and elevation of caspase 1p10 expression. Taken all together, it is deduced that, mechanistically, the upregulation of PPARγ by CLAGS4 of P. pentosaceus GS4 can alter cancer cell metabolism in association with triggering apoptosis in CC.

Characterization and evaluation of the therapeutic benefits of pure and lanthanides mono- and co-doped zinc oxide nanoparticles

The effect of Lanthanides-doping on the structural, optical, morphological, antibacterial and anticancer properties of zinc oxide (ZnO) nanoparticles was investigated. Pure ZnO, Zn0.9La0.1O, Zn0.9Ce0.1O, and Zn0.9La0.05Ce0.05O were fabricated through the chemical co-precipitation route. The structural and morphological properties were studied using the X-ray diffraction (XRD) and transmission electron microscopy (TEM), respectively. The optical properties were analyzed by photoluminescence spectroscopy (PL). The inhibitory effect of the synthesized nanoparticles (NPs) was assessed against six bacterial strains using the agar well diffusion and broth micro-dilution methods. The anticancer potential of the synthesized NPs was assessed against two human colon cancer cell lines Caco-2 and HCT-116. The appearance of the La2O3 and CeO2 secondary phases upon doping La3+ and Ce3+ ions induced structural and morphological changes. The large distorted hexagonal morphology of pure ZnO is transformed into small sized distorted hexagonal form. The photoluminescence spectra revealed the point defects resulting from Lanthanum (La) and cerium (Ce) doping. The prepared NPs significantly inhibited the growth of the six investigated bacteria and induced cytotoxic effects and morphological changes against Caco-2 and HCT-116 cell lines. This study showed that doping ZnO with lanthanide ions such as La3+ and Ce3+ provide promising biological applications. These NPs showed a potent antibacterial and anticancer effect towards the investigated bacterial strains and colon cancer cell lines. These findings point to the importance of the biological applications of NPs, and the possibility of investigating other biomedical applications for NPs.

Soluble peptidoglycan fragments produced by Limosilactobacillus fermentum with antiproliferative activity are suitable for potential therapeutic development: A preliminary report.

Currently, the use of probiotic strains and their products represents a promising innovative approach as an antagonist treatment against many human diseases. Previous studies showed that a strain of Limosilactobacillus fermentum (LAC92), previously defined as Lactobacillus fermentum, exhibited a suitable amensalistic property. The present study aimed to purify the active components from LAC92 to evaluate the biological properties of soluble peptidoglycan fragments (SPFs). The cell-free supernatant (CFS) and bacterial cells were separated after 48h of growth in MRS medium broth and treated for isolation of SPFs. Antimicrobial activity and proliferation analysis on the human cell line HTC116 were performed using technologies such as xCELLigence, count and viability, and clonogenic analysis. MALDI-MS investigation and docking analysis were performed to determine the molecular structure and hypothetical mode of action, respectively. Our results showed that the antimicrobial activity was mainly due to SPFs. Moreover, the results obtained when investigating the SPF effect on the cell line HCT116 showed substantial preliminary evidence, suggesting their significant cytostatic and quite antiproliferative properties. Although MALDI was unable to identify the molecular structure, it was subsequently revealed by analysis of the bacterial genome. The amino acid structure is called peptide 92. Furthermore, we confirmed by molecular docking studies the interaction of peptide 92 with MDM2 protein, the negative regulator of p53. This study showed that SPFs from the LAC92 strain exerted anticancer effects on the human colon cancer HCT116 cell line via antiproliferation and inducing apoptosis. These findings indicated that this probiotic strain might be a potential candidate for applications in functional products in the future. Further examination is needed to understand the specific advantages of this probiotic strain and improve its functional features to confirm these data. Moreover, deeper research on peptide 92 could increase our knowledge and help us understand if it will be possible to apply to specific diseases such as CRC.

In vitro antioxidant, anti-inflammatory, and anticancer activities of mixture Thai medicinal plants

BackgroundThe phytochemical study of medicinal plants is rapidly gaining popularity with many pharmacologic effects. This study aims to determine the antioxidant capacity as well as anticancer and antimigration activities of Clear belongs Plus extract (CBL-P) which consisted of five medicinal plants namely, Alpinia galanga, Piper nigrum, Citrus aurantifolia, Tiliacora triandra, and Cannabis sativa on human colon cancer cells SW620 and HCT116 cell lines, and human non-small cell lung cancer cells A549 and NCI-H460 cell lines.MethodsIn this study the dried-plant powder was extracted using 90% ethanol. Additionally, CBL-P was studied antioxidative activity via DPPH and ABTS assays and anti-inflammatory activities using nitric oxide assay using Griess reaction. Antiproliferation and antimigration of CBL-P were investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and scratch assay.ResultsThe results showed that CBL-P had potent antiproliferative activity with IC50 values in a concentration- and time-dependent manners for all four cell lines. CBL-P also possessed potent antimigration activity against all studied cancer cells. CBL-P demonstrated antimigration activity on four different types of cancer cells (A549, NCI-H460, HCT116, and SW620) after 48 h of incubation, with the greatest effect seen at the highest concentration tested (15 μg/mL) in A549 cells (10.23% of wound closure) and NCI-H460 cells (9.16% of wound closure). CBL-P was also effective in reducing migration in HCT116 and SW620 cells, with a range of closure area from 10—50%. In addition, CBL-P had antioxidant activity with IC50 values of 8.549 ± 0.241 mg/mL and 2.673 ± 0.437 mg/mL for DPPH and ABTS assays, respectively. CBL-P also showed anti-inflammatory activity with the best inhibitory activity on NO production at a concentration of 40 μg/mL.ConclusionIn conclusion, the mixture extract possessed antioxidant and anti-inflammatory activity. Furthermore, the mixture plant extract significantly exhibited antiproliferative and antimigration activities on SW620, HCT116, A549, and NCI-H460 cells (P ≤ 0.05). Taken together, our results suggest that medicinal plants may have synergistic effects that could potentially enhance the effectiveness of cancer treatment when used as adjuvants. These findings provide a solid scientific foundation for future efforts to explore the mechanism of action.

Design, Physical Characterizations, and Biocompatibility of Cationic Solid Lipid Nanoparticles in HCT-116 and 16-HBE Cells: A Preliminary Study.

In this study, pEGFP-LUC was used as a model plasmid and three distinct cationic lipids (dioleyloxy-propyl-trimethylammonium chloride [DOTMA], dioleoyl trimethylammonium propane [DOTAP], and cetylpyridinium chloride [CPC]) were tested along with PEG 5000, as a nonionic surfactant, to prepare glyceryl monostearate (GMS)-based cationic solid lipid nanoparticles (cSLNs). Both the type and quantity of surfactant had an impact on the physicochemical characteristics of the cSLNs. Thermal analysis of the greater part of the endothermic peaks of the cSLNs revealed they were noticeably different from the individual pure compounds based on their zeta potential (ZP ranging from +17 to +56 mV) and particle size (PS ranging from 185 to 244 nm). The addition of cationic surfactants was required to produce nanoparticles (NPs) with a positive surface charge. This suggested that the surfactants and extensive entanglement of the lipid matrix GMS provided support for the behavioral diversity of the cSLNs and their capacity to interface with the plasmid DNA. Additionally, hemolytic assays were used to show that the cSLNs were biocompatible with the human colon cancer HCT-116 and human bronchial epithelial 16-HBE cell lines. The DOTMA 6-based cSLN was selected as the lead cSLN for further ex vivo and in vivo investigations. Taken together, these new findings might provide some guidance in selecting surfactants to prepare extremely efficient and non-toxic cSLN-based therapeutic delivery systems (e.g., gene therapy).

A PRECLINICAL STUDY ON EVALUATION OF ANTICANCER ACTIVITY OF SNUHI KSHARA IN HUMAN COLON CANCER CELL LINE HCT-15

Snuhi (Euphorbia neriifolia Linn.) is a conventional herb used broadly in several disease conditions as indicated in classical texts of Ayurveda. As per literature review ascertained, no literature was accessible regarding anticancer activity of Snuhi Kshara. Thus, present work was designed to evaluate the anticancer activity of Snuhi Kshara in HCT-15 (Human Colon Cancer cell line). Anticancer activity was evaluated using MTT assay by % cell viability and IC50. Anticancer activity was compared with standard drug capecitabine. A positive correlation between Concentration and % cell viability was noticed. Lowest cell viability was noted at 5000 µg concentration. Results obtained through the study indicates towards anticancer activity of Snuhi Kshara

High therapeutic efficacy of 5-Fluorouracil-loaded exosomes against colon cancer cells.

The successful chemotherapeutic regime required for the clinical management of different cancers largely depends on the efficient drug delivery within the cancer cells. Exosomes have emerged as an enticing candidate for exploring their role as delivery vehicles. Exosomes are reported to be intrinsically nanosized vesicles competent for efficient delivery across the cellular membrane. In the present study, we assessed the feasibility of an autologous exosome-based drug delivery platform for delivering 5-Fluorouracil (5-FU) against human colon cancer HCT116 cells. Autologous exosomes have shown probable tropism toward the tumor microenvironment, which makes them the most competitive vehicle for drug delivery. It was observed that the autologous exosomes loaded with 5-FU showed an enhanced rate of drug release under acidic conditions. The result of the cell viability assay showed that treatment of 5-FU-loaded exosomes (equivalent to 5μg 5-FU) resulted in enhanced cytotoxic effect in HCT116 cells as compared to an equivalent amount of free 5-FU (5μg), which elucidated the efficient delivery of the 5-FU by exosomes inside the cancer cells. Subsequently, 5-FU-loaded exosomes led to increased nuclear condensation and fragmentation along with increased ROS production. In addition, 5-FU-loaded exosomes caused enhanced dissipation of mitochondrial membrane potential and caspase-3 activation, resulting in increased apoptosis induction. Our study also revealed that 5-FU-loaded exosomes upsurged the arrest in the cell cycle at the G0/G1 stage in HCT-116 cells and it was found to be associated with decreased CDK4 and Cyclin D1 expression concomitantly with the upregulation of CDK inhibitor, p21Cip1 expression. Thus, the findings from the present study highlight the advantages of autologous exosomes as a natural drug carrier which could efficiently deliver chemotherapeutic drugs to cancer cells.

Effect of Extraction Solvent and Harvest Time on Recovery of Bioactive Com-pounds, Antioxidant and Cancer Cell Growth Inhibition Activities of Korean Ca-mellia mistletoe

This study aimed to determine the phytochemical profiles,in vitroantioxidant and antiproliferative properties of KoreanCamellia mistletoe(Korthalsella japon-ica(Thunb.) Engl.) depending on the harvest time (August and November) and sol-vent (100% methanol, 70% ethanol, and hot water). TheCamellia japonicaL. mistle-toe extracts were analyzed for total phenol, flavonoid, carotenoid, and L-ascorbic acid contents and antioxidant properties such as scavenging capacities (1,1-diphenyl-2-pic-rylhydrazyl (DPPH) and NO•),ferrous ion chelating and reducing power. Concur-rently, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as-say was used to assess the antiproliferative properties against human cancer cell lines; MCF (human breast cancer cells), HeLa (human cervical cancer cells), A375 (human malignant melanoma cells), HCT116 (human colon cancer cells), HepG2 (human liver cancer cells) and A549 (human non-small cell lung adenocarcinoma cells). The results showed that extraction solvent and harvest time had significant impacts on antioxidant and anticancer activities and selectivity for free phenolic compounds inCamellia ja-ponicaL. mistletoe. Among all the tested extracts, the highest amounts of total phe-nolic and total flavonoids content were found in ethanol extracts ofCamellia japon-icaL. mistletoe harvested in November, while the methanol extracts ofCamellia ja-ponicaL. mistletoe collected in August showed the highest contents of total carote-noids and L-ascorbic acidscompared to the other tested extracts. Additionally, the highest NO•radical scavenging activity was found in ethanol extracts, whereas the strongest DPPH radical scavenging activity was found in methanol extracts ofCamel-lia japonicaL. mistletoe harvested in November. Furthermore, methanol extracts showed much higher antiproliferative activity against all human cancer cells than eth-anol extracts ofCamellia japonicaL. mistletoe harvested in November. In conclusion, the antioxidant and anticancer properties ofCamellia japonicaL. mistletoe showed significant dependence on the extraction solvent type and harvest time. With optimum harvest time and extraction solvent, they boast a wide range of promising medical, pharmaceutical, and food applications

Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer.

The anti-inflammatory drug celecoxib, the only inhibitor of cyclooxygenase-2 (COX-2) with anticancer activity, is used to treat rheumatoid arthritis and can cause endoplasmic reticulum (ER) stress by inhibiting sarco/ER Ca2 +-ATPase activity in cancer cells. This study aimed to investigate the correlation between celecoxib-induced ER stress and the effects of celecoxib against cell death signaling. Treatment of human colon cancer HCT116 cells with celecoxib reduced their viability and resulted in a loss of mitochondrial membrane potential ([Formula: see text]). Additionally, celecoxib treatment reduced the expression of genes involved in mitochondrial biogenesis and metabolism such as mitochondrial transcription factor A (TFAM) and uncoupling protein 2 (UCP2). Furthermore, celecoxib reduced transmembrane protein 117 (TMEM117), and RNAi-mediated knockdown of TMEM117 reduced TFAM and UCP2 expressions. These results suggest that celecoxib treatment results in the loss of [Formula: see text] by reducing TMEM117 expression and provide insights for the development of novel drugs through TMEM117 expression.

Synthesis of 1-O-acyl- and 1-oxo-kamebanin analogues and their cytotoxic activity

A series of 1-O-acyl- and 1-oxo-kamebanin analogues were prepared from kamebanin, isolated from Rabdosia excisa and their cytotoxicity was assayed on HL60 promyelocytic leukemia cells and HCT116 human colon cancer cells. The structure–activity relationship study showed that the presence of 1-O-acyl groups of a C3–C5 carbon chain increased the cytotoxic activity.

Green Synthesis of Silver Nanoparticles Using Salvia verticillata and Filipendula ulmaria Extracts: Optimization of Synthesis, Biological Activities, and Catalytic Properties.

The study's objective was to obtain silver nanoparticles (SVAgNP and FUAgNP) using aqueous extracts of Salvia verticillata and Filipendula ulmaria. The optimal conditions for nanoparticle synthesis were determined and obtained; nanoparticles were then characterized using UV-Vis, Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), Dynamic Light Scattering (DLS), Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM/EDS). SVAgNP and FUAgNP possessed a crystalline structure with 48.42% and 60.41% silver weight, respectively. The highest percentage of nanoparticles in the solution had a diameter between 40 and 70 nm. In DPPH˙ and ABTS˙+ methods, FUAgNP (IC50 15.82 and 59.85 µg/mL, respectively) demonstrated a higher antioxidant capacity than SVAgNP (IC50 73.47 and 79.49 µg/mL, respectively). Obtained nanoparticles also showed pronounced antibacterial activity (MIC ˂ 39.1 µg/mL for most of the tested bacteria), as well as high biocompatibility with the human fibroblast cell line MRC-5 and significant cytotoxicity on some cancer cell lines, especially on the human colon cancer HCT-116 cells (IC50 31.50 and 66.51 µg/mL for SVAgNP and FUAgNP, respectively). The nanoparticles demonstrated high catalytic effectiveness in degrading Congo red dye with NaBH4. The results showed a rapid and low-cost methodology for the synthesis of AgNPs using S. verticillata and F. ulmaria with promising biological potential.

β-Sitosterol blocks the LEF-1-mediated Wnt/β-catenin pathway to inhibit proliferation of human colon cancer cells

ObjectivesThis study aimed to investigate the LEF-1-mediated Wnt/β-catenin pathway for its biological functions and prognostic value in colon cancer (CC). Furthermore, the potential molecular mechanism of β-sitosterol in CC was investigated in vitro. MethodsClinical information and gene expression profiles from CC patients were obtained based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, we applied R software “Limma” package for the differential analysis of LEF-1 between cancer and para-carcinoma tissue samples. Kaplan–Meier (KM) survival analysis was adopted for analyzing whether LEF-1 was of prognostic significance. Moreover, gene set enrichment analysis (GSEA) was adopted for pathway enrichment analysis and visualization. In addition, CCK8, plate cloning, scratch and high-content screening (HCS) imaging assays were performed to examine the therapeutic efficacy of β-sitosterol in human CC HCT116 cells. siRNA technology was employed to knock down LEF1 expression in HCT116 cells. qRT-PCR and Western-blot (WB) analysis were carried out to analyze the HCT-116 mRNA and protein expression levels, respectively. ResultsLEF-1 was up-regulated within CC and acted as an oncogenic gene. LEF-1 up-regulation predicted the dismal prognostic outcome and activated the Wnt/β-catenin pathway. β-sitosterol effectively suppressed HCT116 cells proliferation and invasion. For the mechanism underlying β-sitosterol, β-sitosterol was found to significantly down-regulate LEF-1 gene and protein expression and disrupt Wnt/β-catenin pathway transmission in HCT116 cells. After suppressing LEF-1 expression, its downstream targets including C-myc, Survivin and CCND1 were also down-regulated. ConclusionAccording to our results, LEF-1 down-regulation can effectively block Wnt/β-catenin pathway, inhibit CC cell growth and migration. Collectively, β-sitosterol can be used to treat CC, which can provide anti-tumor activity by targeting LEF-1.

Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification

ABSTRACT The possible anticancer activity of combination (M + E + F) of metformin (M), efavirenz (E), and fluoxetine (F) was investigated in normal HDF cells and HCT116 human colon cancer cells. Metformin increased cellular FOXO3a, p-FOXO3a, AMPK, p-AMPK, and MnSOD levels in HDFs but not in HCT116 cells. Cellular ATP level was decreased only in HDFs by metformin. Metformin increased ROS level only in HCT116 cells. Transfection of si-FOXO3a into HCT116 reversed the metformin-induced cellular ROS induction, indicating that FOXO3a/MnSOD is the key regulator for cellular ROS level. Viability readout with M, E, and F alone decreased slightly, but the combination of three drugs dramatically decreased cell survival in HCT116, A549, and SK-Hep-1 cancer cells but not in HDF cells. ROS levels in HCT116 cells were massively increased by M + E + F combination, but not in HDF cells. Cell cycle analysis showed that of M + E + F combination caused cell death only in HCT116 cells. The combination of M + E + F reduced synergistically mitochondrial membrane potential and mitochondrial electron transport chain complex I and III activities in HCT116 cells when compared with individual treatments. Western blot analysis indicated that DNA damage, apoptosis, autophagy, and necroptosis-realated factors increased in M + E + F-treated HCT116 cells. Oral administration with M + E + F combination for 3 weeks caused dramatic reductions in tumor volume and weight in HCT116 xenograft model of nude mice when compared with untreated ones. Our results suggest that M + E + F have profound anticancer activity both in vitro and in vivo via a cancer cell-specific ROS amplification (CASRA) through ROS-induced DNA damage, apoptosis, autophagy, and necroptosis.

Agrimol B inhibits colon carcinoma progression by blocking mitochondrial function through the PGC-1α/NRF1/TFAM signaling pathway.

The activation of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) stimulates the transcription of the downstream target proteins, mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1), which induces mitochondrial biogenesis and promotes colorectal tumorigenesis. Agrimol B (Agr) is a constituent of Agrimonia pilosa Ledeb. that exerts anticancer effects. Herein, we aimed to investigate the antitumor activity of Agr and its mechanism of action. The interaction between Agr and PGC-1α was predicted by molecular docking. After the treatment with different concentrations of Agr (0, 144, 288, and 576 nM), the cell viability, migration rate, proliferation rate, and apoptosis rate of human colon cancer HCT116 cells were determined. Mitochondrial activity, cellular reactive oxygen species (ROS), and mitochondrial membrane potential were assessed to measure the regulatory effect of Agr on mitochondrial function. Western blotting (WB) assay was used to examine the expression of PGC-1α, NRF1, and TFAM, as well as of the pro-apoptotic proteins, Bax and Caspase-3, and the antiapoptotic protein (Bcl-2). Finally, subcutaneous tumor xenograft model mice were used to evaluate the effect of Agr on colorectal cancer (CRC) in vivo. The molecular docking results revealed a high likelihood of Agr interacting with PGC-1α. Agr inhibited the proliferation and migration of HCT116 cells, promoted ROS production and mitochondrial oxidative stress, inhibited mitochondrial activity, and decreased mitochondrial membrane potential. Agr induced cell apoptosis and, in combination with PGC-1α, impaired mitochondrial biogenesis and suppressed the expression of NRF1 and TFAM. Agr also suppressed the expression of Bcl-2 and Cleaved-Caspase-3 and increased the expression of Bax and Caspase-3. In addition, the in vivo antitumor effect and mechanism of Agr were confirmed by using a subcutaneous tumor xenograft mouse model. Our findings demonstrated that Agr regulates the expression of PGC-1α, thereby inducing mitochondrial dysfunction and promoting tumor cell apoptosis. This work highlights the potential of Agr as a promising therapeutic candidate in CRC.

β-elemene regulates epithelial-mesenchymal transformation and inhibits invasion and metastasis of colorectal cancer cells.

To study the inhibitory effect of β-elemene on invasion and metastasis of colorectal cancer cells and its possible mechanism. Human colon cancer HCT116 cells were treated with different concentrations of β-elemene. The proliferation inhibition rate of the cells was detected by MTT assay, cell migration rate was detected by scratched assay, andcell invasion rate was evaluated by Transwell cell invasion assay. The expressions of Vimentin, E-cadherin, N-cadherin, and β-catenin were detected by Western blotting. The mRNA expressions of Vimentin, E-cadherin, N-cadherin, and β-catenin were detected by real-time PCR. Compared with the control group, the expressions of migration rate, invasion rate, scratch healing rate, N-cadherin, and Vimentin protein of HCT116 cells were decreased after β-elemene treatment, while the expression of E-cadherin protein was increased, and the inhibition rate of cell proliferation was increased (p<0.05). β-elemene may inhibit cell proliferation and invasion and metastasis by inhibiting EMT signaling pathway in human colon cancer cell line HCT116.

Hydrothermal Synthesis of Multifunctional Bimetallic Ag-CuO Nanohybrids and Their Antimicrobial, Antibiofilm and Antiproliferative Potential.

The rapidly growing global problem of infectious pathogens acquiring resistance to conventional antibiotics is an instigating reason for researchers to continue the search for functional as well as broad-spectrum antimicrobials. Hence, we aimed in this study to synthesis silver-copper oxide (Ag-CuO) nanohybrids as a function of Ag concentration (0.05, 0.1, 0.3 and 0.5 g) via the one-step hydrothermal method. The bimetallic Ag-CuO nanohybrids Ag-C-1, Ag-C-2, Ag-C-3 and Ag-C-4 were characterized for their physico-chemical properties. The SEM results showed pleomorphic Ag-CuO crystals; however, the majority of the particles were found in spherical shape. TEM results showed that the Ag-CuO nanohybrids in formulations Ag-C-1 and Ag-C-3 were in the size range of 20-35 nm. Strong signals of Ag, Cu and O in the EDX spectra revealed that the as-synthesized nanostructures are bimetallic Ag-CuO nanohybrids. The obtained Ag-C-1, Ag-C-2, Ag-C-3 and Ag-C-4 nanohybrids have shown their MICs and MBCs against E. coli and C. albicans in the range of 4-12 mg/mL and 2-24 mg/mL, respectively. Furthermore, dose-dependent toxicity and apoptosis process stimulation in the cultured human colon cancer HCT-116 cells have proven the Ag-CuO nanohybrids as promising antiproliferative agents against mammalian cancer.