Human Colon Adenocarcinoma Research Articles

Use of Small-molecule Inhibitory Compound of PERK-dependent Signaling Pathway as a Promising Target-based Therapy for Colorectal Cancer.

Colorectal cancer constitutes one of the most common cancer with a high mortality rate. The newest data has reported that activation of the pro-apoptotic PERK-dependent unfolded protein response signaling pathway by small-molecule inhibitors may constitute an innovative anti-cancer treatment strategy. In the presented study, we evaluated the effectiveness of the PERK-dependent unfolded protein response signaling pathway small-molecule inhibitor 42215 both on HT-29 human colon adenocarcinoma and CCD 841 CoN normal human colon epithelial cell lines. Cytotoxicity of the PERK inhibitor was evaluated by the resazurin-based and lactate dehydrogenase (LDH) tests. Apoptotic cell death was measured by flow cytometry using the FITCconjugated Annexin V to indicate apoptosis and propidium iodide to indicate necrosis as well as by colorimetric caspase-3 assay. The effect of tested PERK inhibitor on cell cycle progression was measured by flow cytometry using the propidium iodide staining. The level of the phosphorylated form of the eukaryotic initiation factor 2 alpha was detected by the Western blot technique. Obtained results showed that investigated PERK inhibitor is selective only toward cancer cells, since inhibited their viability in a dose- and time-dependent manner and induced their apoptosis and G2/M cell cycle arrest. Furthermore, 42215 PERK inhibitor evoked significant inhibition of eIF2α phosphorylation within HT-29 cancer cells. Highly-selective PERK inhibitors may provide a ground-breaking, anti-cancer treatment strategy via activation of the pro-apoptotic branch of the PERK-dependent unfolded protein response signaling pathway.

5-aminopyrazole-conjugated gelatin hydrogel: A controlled 5-fluorouracil delivery system for rectal administration

In recent years, more interest was dedicated to drug delivery systems (DDSs) and targeting drugs to the colonic region of the gastrointestinal tract. For this purpose, 5-aminopyrazole-conjugated gelatin hydrogel (5-AP/G) was designed to load anticancer 5-fluorouracil (5-FU) drug through soaking in the solution of drug. By using various analyses, the prepared 5-AP/G was characterized. In-vitro drug release study was carried out in simulating the rectal conditions for establishing the productivity of the prepared novel anticancer agent. 5-AP/G showed a predictable drug release manner in the rectal conditions with notable cytotoxicity against human colon adenocarcinoma HT29 cells. According to the obtained results, 5-AP/G hydrogel as a rectal administration of 5-FU could potentially be proposed in DDS for the treatment of rectal cancer.

Phytochemical Screening and Cytotoxic Properties of Ethanolic Extract of Young and Mature Khat Leaves

The khat plant has been culturally used in many parts of Africa and the Arabian Peninsula for many years to induce psycho-stimulating effect. Because of the global wide-spreading nature, khat chewing is being considered as a universally growing problem. Catha abbottii, Catha edulis, and Catha transvaalensis are the three species of khat commonly chewed in Saudi Arabia and nearby regions. Khat users usually prefer to chew young leaves over mature ones due to the diverse effects produced by both. Though many of the constituents of khat leaves have been identified, the complete phytochemical profile of young and mature leaves was not performed or compared; also, no evidence is available to affirm the cytotoxicity of young or mature leaves. Therefore, this study aimed to investigate the phytochemical basis of the differential response of the young and mature leaves and to assess the cytotoxicity of young and mature khat leaves. Ethanolic extracts of young and mature leaves of three khat cultivars were subjected to GC-MS. Hierarchical cluster analysis revealed the existence of two major clusters. The extracts of young leaves were found to contain the maximum content of cathinone; however, methoxyamphetamine was found in only one extract of young leaves. Cytotoxicity investigations were also conducted on both types of leaves using three cancer cell lines, human breast adenocarcinoma, human ovary adenocarcinoma, and human colon adenocarcinoma and also normal human fetal lung fibroblast cell line was used. All extracts showed comparable cytotoxicity, IC50 ranging from 22–59 μg/mL on the cancer cells; however, we observed more cytotoxicity against normal cells (IC50: 6–41 μg/mL). The predominant cytotoxicity on normal cells may pose many health hazards to khat consumers.

In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment.

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.

A New NT4 Peptide-Based Drug Delivery System for Cancer Treatment.

The development of selective tumor targeting agents to deliver multiple units of chemotherapy drugs to cancer tissue would improve treatment efficacy and greatly advance progress in cancer therapy. Here we report a new drug delivery system based on a tetrabranched peptide known as NT4, which is a promising cancer theranostic by virtue of its high cancer selectivity. We developed NT4 directly conjugated with one, two, or three units of paclitaxel and an NT4-based nanosystem, using NIR-emitting quantum dots, loaded with the NT4 tumor-targeting agent and conjugated with paclitaxel, to obtain a NT4-QD-PTX nanodevice designed to simultaneously detect and kill tumor cells. The selective binding and in vitro cytotoxicity of NT4-QD-PTX were higher than for unlabeled QD-PTX when tested on the human colon adenocarcinoma cell line HT-29. NT4-QD-PTX tumor-targeted nanoparticles can be considered promising for early tumor detection and for the development of effective treatments combining simultaneous therapy and diagnosis.

Green Synthesis of Zinc Oxide Nanoparticles Using Aqueous Extract of Deverra tortuosa and their Cytotoxic Activities

In recent years, there is a growing interest towards the green synthesis of metal nanoparticles, particularly from plants; however, yet no published study on the synthesis of ZnO.NPs using the Deverra tortuosa extract. Through this study, zinc oxide nanoparticles (ZnO.NPs) have been synthesized based on using the environmentally benign extract of the aerial parts of D. tortuosa as a reducing and capping agent. ZnO.NPs synthesis was confirmed using UV-Visible (UV-Vis) spectroscopy, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD) and High Resolution-Transmission Electron Microscope (HR-TEM). The qualitative and quantitative analyses of plant extract were done. The potential anticancer activity was in vitro investigated against two cancer cell lines (human colon adenocarcinoma “Caco-2” and human lung adenocarcinoma “A549”) compared to their activities on the human lung fibroblast cell line (WI38) using the MTT assay. Both the aqueous extract and ZnO.NPs showed a remarkable selective cytotoxicity against the two examined cancer cell lines.

Pro-apoptotic action of protein-carbohydrate fraction isolated from coelomic fluid of the earthworm Dendrobaena veneta against human colon adenocarcinoma cells

Earthworm coelomic fluid (CF) is known as a rich source of various bioactive compounds with promising anticancer features. However, it has been demonstrated that CF affects functionality of both, cancer and normal cells. This non-selective activity causes a major problem for medical application of CF.In this study, we present the anticancer activity of the active protein-carbohydrate fraction (AF) isolated from thermally treated CF of earthworm Dendrobaena veneta. The in vitro effect of the AF was examined in human colon model including normal human colon epithelium (CCD 841 CoTr) and human colon adenocarcinoma (HT-29 and LS180) cell lines. We investigated the impact of AF on cell viability neutral red and lactate dehydrogenase assays, morphology May-Grünwald-Giemsa staining assay proliferation MTT tetrazolium salt and BrdU incorporation assays as well as cell cycle progression propidium iodide/RNase staining and the activity of human 20S proteasome the hydrolysis of AMC from a Suc-LLVY-AMC peptide substrate. Additionally, the influence of AF on apoptosis was examined in HT-29 cells by Annexin V/PI, Hoechst 33342 staining and active caspase-3 assays.Our investigation demonstrated that AF at the tested concentration range does not affect the viability and morphology of CCD 841 CoTr cells. Simultaneously, AF inhibits human 20S proteasome activity as well as significantly decreases mitochondrial metabolism, disturbs cell cycle and induces apoptosis via activation of procaspase-3 in HT-29 cancer cells. Obtained results demonstrate the antiproliferative and proapoptotic activity of AF that can be useful in developing therapeutic strategies to treat human colon cancer.

Absorption Rates and Mechanisms of Avenanthramides in a Caco-2 Cell Model and Their Antioxidant Activity during Absorption.

Avenanthramides (AVNs) are a unique kind of polyphenols that were only detected in the oats and have been demonstrated to exhibit strong antioxidant activities but low bioavailability. The purpose of the present research was to evaluate the absorption rates and mechanisms of AVNs (AVN 2c, AVN 2f, and AVN 2p) using a human colon adenocarcinoma cell line (Caco-2) cell model and clarify the influence of the absorption process on the antioxidant capacities of AVNs. Furthermore, the absorption rates and antioxidant activities of ferulic acid and caffeic acid were compared with those of AVNs. Results showed that the apparent absorption rates (Papp) of AVN 2c, AVN 2f, and AVN 2p were 0.65 ± 0.05 × 10-6, 1.18 ± 0.16 × 10-6, and 1.44 ± 0.09 × 10-6 cm/s, respectively, which were significantly lower than those of caffeic acid (3.76 ± 0.31 × 10-6 cm/s) and ferulic acid (1.69 ± 0.13 × 10-5 cm/s). Moreover, the metabolites (caffeic acid, ferulic acid, and AVN 2f) of AVNs after absorption were detected and quantified by high-performance liquid chromatography-mass spectrometry. Before absorption, although the antioxidant capacities of AVNs were significantly stronger than those of ferulic acid and caffeic acid, there was an opposite result after absorption. In addition, AVNs transported the Caco-2 monolayer by paracellular diffusion and were affected by monoamine oxidase and efflux transporters (P-gp, MRP2) during absorption. The co-administration of quercetin could significantly improve the absorption rates of AVNs.

Characteristics and bioactive properties of mannooligosaccharides derived from agro-waste mannans

Mannooligosaccharides (MOS) were derived using Aspergillus oryzae β-mannanase (ManAo) from different mannan-rich agro-wastes, palm kernel cake (PKC), guar gum and copra meal (CM). Guar gum (GG) released higher amount of MOS (56.31% w/w) from which purification of mannobiose (0.68 mg) and mannotriose (1.26 mg) was demonstrated using size-exclusion chromatography. FTIR analysis of mannan hydrolysates showed characteristic peaks in 1200–900 cm−1 region indicating the presence of MOS. 1H &13C NMR spectra showed presence of anomeric sugar forms of MOS in different mannan hydrolysates. MOS from locust bean gum and guar gum had both α- and β-anomers while PKC and CM had only α-anomer. Growth promotional activities of different MOS were demonstrated using two probiotic Lactobacilli. Besides, enzymatically derived MOS also showed metal (Fe2+) chelating and anti-oxidant activities, wherein best anti-glycating agent was evaluated as MOS from PKC. PKC derived MOS showed highest cytotoxicity (74.19%) against human colon adenocarcinoma cell line (Caco-2). This study demonstrated the prebiotic potential of agro-waste derived MOS and possibility of their utilization as a functional food ingredient.

Chemical composition of the Brazilian native Cinnamomum stenophyllum (Meisn.) Vattimo-Gil essential oil by GC-qMS and GC × GC-TOFMS, and its cytotoxic activity

Cinnamomum stenophyllum (Meisn.) Vattimo-Gil (Lauraceae) is a native and vulnerable Brazilian species restricted to the Atlantic Forest. The leaf essential oil obtained by hydrodistillation was characterized for the first time by two-dimensional gas chromatography with time-of-flight mass spectrometry (GC × GC-TOFMS). This analysis resulted in the tentatively identification of 80 compounds, showing the superior performance of this method in comparison to the seven compounds identified by GC–MS. The identified compounds included 8 ketones, 7 monoterpene hydrocarbons, 30 oxygenated monoterpenes, 4 sesquiterpene hydrocarbons and 23 oxygenated sesquiterpenes, showing that the C. stenophyllum oil contained mostly oxygenated mono and sesquiterpenes. The oil cytotoxicity was tested against two human cancer cell lines, colon adenocarcinoma (HCT-116) and breast cancer carcinoma (MCF-7), and the non-tumor retinal pigment epithelial cells (RPE) using the colorimetric MTT assay. Both cancer cell lines were sensible to leaf essential oil, with IC50 < 20 μg/mL (HCT, IC50 = 9.95 μg/mL and MCF-7, IC50 = 16.65 μg/mL), while there was no cytotoxicity against the non-tumor cells at tested concentrations (IC50 > 50 μg/mL), suggesting selectivity to cancer cells. The results showed that the C. stenophyllum leaf essential oil has a cytotoxic potential, presenting several compounds already known as biologically active against tumor cells.

A lectin with anti-microbial and anti proliferative activities from Lantana camara, a medicinal plant

BackgroundLectins are known to possess interesting biological properties such as anti microbial, nematicidal, anti tumor and anti viral activities. Lantana camara from verbenaceae family is a medicinal plant known for possessing anti oxidant and anticancer activities. Since anticancer activity is reported in plant lectins, leaves of Lantana camara was used to check the presence of lectin. Methods and resultsHere we report the purification, characterization and biological properties of a lectin from Lantana camara (LCL) leaves. LCL was purified by ion exchange chromatography on CM-cellulose column followed by affinity chromatography on mucin coupled Sepharose 4B column and gel filtration chromatography on Superdex G75 column. LCL is a glycoprotein with 10% of the carbohydrate and is blood group non specific. SDS-PAGE analysis of affinity purified LCL showed two proteins with apparent molecular weight of 14.49 kDa and 17.4 kDa which were subsequently separated by Gel filtration chromatography on Superdex G75 column. Hapten inhibition studies of LCL revealed its highest affinity for Chitin, Milibiose, α-D-Methyl galactopyranoside and glycoproteins like mucin, asialomucin. LCL showed strong binding to human colon adenocarcinoma HT29 cells with MFI of 242 which was effectively blocked by 68.1 and 62.5% by both mucin and milibiose. LCL showed dose and time dependent growth inhibitory effects on HT29 cells with IC50 of 3.75 μg/ml at 48 h. LCL has potent antibacterial and anti fungal activity. ConclusionLCL can be explored for its clinical potential.

Acrylamide Decreases Cell Viability, and Provides Oxidative Stress, DNA Damage, and Apoptosis in Human Colon Adenocarcinoma Cell Line Caco-2.

Acrylamide (AA) toxicity remains an interesting subject in toxicological research. The aim of the research performed in this paper was to determine mechanisms of cyto- and genotoxic effects of AA on the human colon adenocarcinoma cell line Caco-2, to estimate the inhibitory concentration (IC)50 values in cell viability assays, to measure the basal and oxidative DNA damage as well as the oxidative stress leading to apoptosis, and to assess the morphological changes in cells using microscopic methods. It has been proven that AA induces cytotoxic and genotoxic effects on Caco-2 cells. Higher cytotoxic activity was gained in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay compared with the PrestoBlue assay, with IC50 values of 5.9 and 8.9 mM after 24 h exposure, respectively. In the single-cell gel electrophoresis assay, the greatest DNA damage was caused by the highest concentration of acrylamide equal to 12.5 mM (89.1% ± 0.9%). AA also induced oxidative DNA damage and generated reactive oxygen species (ROS), which was concentration dependent and correlated with the depletion of mitochondrial membrane potential and apoptosis induction. In the microscopic staining of cells, AA in the dosage close to the IC50 induced morphological changes typical for apoptosis. Taken together, these results demonstrate that AA has a pro-oxidative effect on Caco-2 cells, leading to apoptotic cell death.

Indomethacin and juglone inhibit inflammatory molecules to induce apoptosis in colon cancer cells.

Colorectal cancer (CRC) is the third most common fatal cancer. Indomethacin, a nonsteroidal anti-inflammatory drug, is known to reduce the occurrence of CRC. This study evaluated the potential anticolon cancer effects of juglone (5-hydroxy-1,4-naphthoquinone) in combination with indomethacin. Human colon adenocarcinoma cells (HT29) were subjected to treatment with indomethacin, juglone, and a combination of both. Morphological analysis, cell cycle regulation, and dual staining using acridine orange and ethidium bromide in control and treated cells revealed the apoptotic potential of these compounds. Bcl2 and inflammatory molecules (tumor necrosis factor-α, nuclear factor kappa B, and Cox-2) were found to be decreased with a concomitant increase in the expression of proapoptotic molecules (Bad, Bax, cytochrome c, and PUMA) as a result of the molecular regulation of Wnt, Notch, and peroxisome proliferator-activated receptor-γ signaling. Treatment with juglone was not as effective as with indomethacin; however, a combination of both was shown to be more effective, suggesting that juglone may be considered for therapeutic intervention of colon cancer.

HOXC11 functions as a novel oncogene in human colon adenocarcinoma and kidney renal clear cell carcinoma

AimsAccumulating evidence has confirmed the involvement of the homeobox (HOX) gene family in carcinogenesis. HOXC11, belongs to the homeobox-C (HOXC) gene cluster, has been reported to play important roles in the development of several cancers. However, its expression and clinical value in pan-cancer remain elusive. Materials and methodsBioinformatics analysis, CCK-8 assay, Flow cytometry and Western blot were used to analyze gene expression and patient survival, cell proliferation, cell apoptosis and protein level, respectively. Key findingsIn this study, we comprehensively analyzed the expression profile and prognostic value of HOXC11 in human pan-cancer using online The Cancer Genome Atlas (TCGA) databases. HOXC11 was widely up-regulated in tumor tissues when compared with the normal tissues in pan-cancer across nine cancer types. In addition, high mRNA level of HOXC11 predicted poor overall survival (OS) of patients with adrenocortical carcinoma (ACC), colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), mesothelioma (MESO) and pancreatic adenocarcinoma (PAAD), respectively. By comparative analysis, we found that HOXC11 was up-regulated and closely correlated patient OS in COAD and KIRC. Functionally, down-regulation of HOXC11 inhibited cell proliferation but promoted apoptosis of COAD and KIRC in vitro. Mechanistically, HOXC11 promoted cell proliferation of COAD and KIRC might by inactivating the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. SignificanceOur findings suggest that HOXC11 may act as a tumor driving gene in COAD and KIRC.

Anti-Tumor Activity of Atractylenolide I in Human Colon Adenocarcinoma In Vitro.

Atractylodes macrocephala is known to exhibit multi-arrays of biologic activity in vitro. However, detail of its anti-tumor activity is lacking. In this study, the effects of atractylenolide I (AT-I), a bio-active compound present in Atractylodes macrocephala rhizome was studied in the human colorectal adenocarcinoma cell line HT-29. The results showed that AT-I induced apoptosis of human colon cancer cells through activation of the mitochondria-dependent pathway. The IC50 of AT-I was 277.6 μM, 95.7 μM and 57.4 μM, after 24, 48 and 72 h of incubation with HT-29, respectively. TUNEL and Annexin V-FITC/PI double stain assays showed HT-29 DNA fragmentation after cell treatment with various AT-I concentrations. Western blotting analysis revealed activation of both initiator and executioner caspases, including caspase 3, caspase 7, and caspase 9, as well as PARP, after HT-29 treatment with AT-I via downregulation of pro-survival Bcl-2, and upregulation of anti-survival Bcl-2 family proteins, including Bax, Bak, Bad, Bim, Bid and Puma. The studies show for the first time that AT-I is an effective drug candidate towards the HT-29 cell.

Dextrorotatory Chromomycins from the Marine Streptomyces sp. Associated to Palythoa caribaeorum

A Streptomyces sp. (BRA-384) was selected among nine strains of bacteria isolated from the zoanthids Palythoa caribaeorum due to the high cytotoxic activity presented by its EtOAc extract (inhibitory concentration mean (IC50) of 2 ng mL-1) against colon cancer cell line. From the EtOAc extract of BRA-384 three new chemical entities (A6, A7 and A8) and one dextrorotatory chromomycin (A5), a promising class of anticancer compounds, were identified. The cytotoxicity of chromomycins A5 to A8 was tested against five tumor cell lines (HCT 116 (human colon adenocarcinoma), MCF-7 (human breast carcinoma), PC-3M (human metastatic prostate cancer), 501-mel (human metastatic melanoma) and MM200 (metastatic melanoma)). All chromomycins were highly potent showing IC50 values from 0.2 to 133 nM. Chromomycin A5 was consistently the most potent over all tested cells (IC50 values from 0.2 in MM200 to 7.9 nM in PC-3M), inclusive when compared to the standard chemotherapeutic agent doxorubicin, that presented IC50 values ranging from 147 to 568 nM against MM200 and MCF-7, respectively.

The antioxidant potential of peptides obtained from the spotted babylon snail (Babylonia areolata) in treating human colon adenocarcinoma (Caco-2) cells

This research study investigated the free radical-scavenging activities of peptides which were obtained from the protein hydrolysates of the spotted babylon snail using a combination of pepsin and pancreatin proteolysis which can replicate the conditions of gastrointestinal digestion. In this study, spotted babylon protein hydrolysate (SPH) derived from a sequential 3 hour digestion, first with pepsin and then with pancreatin, was examined. SPH was fractionated using molecular weight cut-off membranes for 10 kDa, 5 kDa, 3 kDa, and 0.65 kDa. It was found that the MW < 0.65 kDa fraction provided the greatest levels of 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazl (DPPH), and nitric oxide (NO) radical scavenging activity. Three subfractions of the MW < 0.65 kDa fraction were then generated via RP-HPLC. The subfraction which subsequently demonstrated the greatest free radical scavenging activity was F3, which was accordingly chosen for further investigation commencing with quadrupole-time-of-flight-electron spin induction-mass spectrometry-based de novo peptide sequencing. This resulted in the identification of a pair of novel peptides: His–Thr–Tyr–His–Glu–Val–Thr–Lys–His (HTYHEVTKH), and Trp–Pro–Val–Leu–Ala–Tyr–His–Phe–Thr (WPVLAYHF). The WPVLAYHF peptide exhibited greater antioxidant activity. The study also confirmed that the F3 sub-fraction was able to prevent hydroxyl radicals from causing DNA damage by conducting tests which involved the pKS, pUC19, and pBR322 plasmids using the Fenton reaction. In addition, cellular antioxidant activity was demonstrated by two synthetic peptides toward the human adenocarcinoma colon (Caco-2) cell line, with the potency of the activity dependent upon the peptide concentration.

Synthesis and Biological Evaluation of Novel Triazolyl-Acridine Derivatives as Cytotoxic Agents

Novel triazolyl-acridine compounds were synthesized in 4 series of 9-(2-(substituted phenyl-1H-1,2,3-triazol-1-yl)ethoxy)acridine, 9-(3-(4-(2-substituted phenyl)-1H-1,2,3-triazol-1-yl)propoxy) acridine, N-(2-(4 substituted phenyl-1H-1,2,3-triazol-1-yl)ethyl)acridin-9-amine and N-(3-(4-(substituted phenyl)-1H-1,2,3-triazol-1-yl)propyl)acridin-9-amine using appropriate synthetic procedures and screened for cytotoxic activity. The structures of all synthesized compounds were confirmed by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance and mass spectroscopy and these compounds were assayed in vitro for cytotoxic activity against MCF-7 (human breast adenocarcinoma cell line) and HT-29 (human colon adenocarcinoma cell line) cells. Tested compounds showed better cytotoxic activities in terms of IC50 value against MCF-7 and HT-29 cells. Methyl substituted compound MPP-9 exhibited excellent sensitivity with IC50 value 1 and 2 µM, against MCF-7 and HT-29, respectively. Unsubstituted MPP-1 and chloro-substituted MPP-2 and MPP-5 also exhibited good IC50 value ranges from 2-4 µM against both cell lines. These compounds were active at micro molar concentrations. Data study revealed that synthesized compounds are promising leads for future as cytotoxic agents.

Oleanolic acid from black raisins, Vitis vinifera with antioxidant and antiproliferative potentials on HCT 116 colon cancer cell line

Vitis vinifera (black raisin) is commonly used in traditional medicine for the treatment of various ailments. In the present study, anti-oxidative and anti-cancer efficacy of oleanolic acid from ethyl acetate fraction of black raisins was evaluated and oleanolic acid was isolated without using of any chromatographic techniques and subjected to spectral assessment using UV-Vis spectrophotometer, 1 H NMR, 13C NMR, MS and FT-IR for structural confirmation. Antiproliferative efficacy of oleanolic acid against human colon adenocarcinoma HCT-116 cells was assessed using cell viability assay. The minimum inhibitory concentration (IC50) was determined and found to be 40 µg/mL at 48h incubation. Furthermore, antioxidant property of oleanolic acid was analyzed using DPPH method (IC50 is 61.5µg/mL) by compared to standard antioxidants ascorbic acid, gallic acid, pyrogallol and butylated hydroxytoluene. Hence, the present study aims to establish the use of oleanolic acid as a potential therapeutic agent against human colon cancer.

Preclinical study of a new 177Lu-labeled somatostatin receptor antagonist in HT-29 human colorectal cancer cells.

Somatostatin receptor-positive neuroendocrine tumors have been targeted using various peptide analogs radiolabeled with therapeutic radionuclides for years. The better biomedical properties of radioantagonists as higher tumor uptake make these radioligands more attractive than agonists for somatostatin receptor-targeted radionuclide therapy. In this study, we tried to evaluate the efficiency of Luthetium-177 (177Lu) radiolabeled DOTA-Peptide 2 (177Lu-DOTA-Peptide 2) as a new radioantagonist in HT-29 human colorectal cancer in vitro and in vivo. DOTA conjugated antagonistic peptide with the sequence of p-Cl-Phe-Cyclo(D-Cys-L-BzThi-D-Aph-Lys-Thr-Cys)-D-Tyr-NH2 (DOTA-Peptide 2) was labeled with 177Lu. In vitro assays (saturation binding assay and internalization test) and animal biodistribution were performed in human colon adenocarcinoma cells (HT-29) and HT-29 tumor-bearing nude mice. 177Lu-DOTA-Peptide 2 showed high stability in acetate buffer and human plasma (>97%). Antagonistic property of 177Lu-DOTA-Peptide 2 was confirmed by low internalization in HT-29 cells (<5%). The desired dissociation constant (Kd =11.14 nM) and effective tumor uptake (10.89 percentage of injected dose per gram of tumor) showed high binding affinity of 177Lu-DOTA-Peptide 2 to somatostatin receptors. 177Lu-DOTA-Peptide 2 demonstrated selective and high binding affinity to somatostatin receptors overexpressed on the surface of HT-29 cancer cells, which could make this radiopeptide suitable for somatostatin receptor-targeted radionuclide therapy.