HT-29 Human Colon Carcinoma Cells Research Articles

Increased Anticancer Activity of Organic Kimchi with Starters Demonstrated in HT-29 Cancer Cells

This study aims to investigate the effects of kimchi made with organic ingredients and lactic acid bacteria (LAB) as starters (Leuconostoc mesenteroides + Lactiplantibacillus plantarum) on HT-29 human colon carcinoma cells. Four types of kimchi (standard kimchi (SK), commercial kimchi (CK), anticancer kimchi (AK), and organic anticancer kimchi (OAK)) were evaluated. The results show that, among the different types of kimchi studied, OAK presents high DPPH free-radical scavenging activity and total phenol and flavonoid contents, and the MTT assay shows that the growth inhibition rate against HT-29 cancer cells is the highest. In addition, the quantitative reverse transcription polymerase chain reaction (RT-qPCR) results show that, compared to SK and CK, AK and OAK can effectively down-regulate the mRNA expression of anti-apoptotic gene Bcl-2 and up-regulate the mRNA expression of the cell cycle arrest genes p21 and p53; pro-apoptotic genes Bim, Bak, and Bad; and genes for caspases 3 9. Subsequently, a Western blot test confirmed that the expression of Bcl-2 decreased and the expressions of p53, Bax, and caspases 3 and 9 increased in OAK. The abovementioned results indicate that the anticancer kimchi prepared with organic ingredients and starters of lactic acid bacteria effectively present the best antioxidant activity and inhibit the proliferation of HT-29 cancer cells by promoting apoptosis and cell cycle arrest.

Design and synthesis of novel ureido and thioureido conjugated hydrazone derivatives with potent anticancer activity

BackgroundCompounds possessing urea/thiourea moiety have a wide range of biological properties including anticancer activity. On the other hand, taking advantage of the low toxicity and structural diversity of hydrazone derivatives, they are presently being considered for designing chemical compounds with hydrazone moiety in the field of cancer treatment. With this in mind, a series of novel ureido/thioureido derivatives possessing a hydrazone moiety bearing nitro and chloro substituents (4a–4i) have been designed, synthesized, characterized and evaluated for their in vitro cytotoxic effect on HT-29 human colon carcinoma and HepG2 hepatocarcinoma cell lines.ResultsTwo compounds (4c and 4e) having the chloro phenylurea group hybridized with phenyl hydrazone bearing nitro or chloro moieties demonstrated potent anticancer effect with the IC50 values between 2.2 and 4.8 µM at 72 h. The mechanism of action of compound 4c was revealed in hepatocellular carcinoma cells as an inducer of apoptosis in a caspase-independent pathway.ConclusionTaken together, the current work presented compound 4c as a potential lead compound in developing future hepatocellular carcinoma chemotherapy drugs.MethodsThe compounds were synthesized and then characterized by physical and spectral data (FT-IR, 1H-NMR, 13C-NMR, Mass). The anticancer activity was assessed using MTT assay, flowcytometry, annexin-V, DAPI staining and Western blot analysis.Graphical

Liquid chromatography coupled to high-resolution mass spectrometry metabolomics: A useful tool for investigating tumor secretome based on a three-dimensional co-culture model.

Three-dimensional (3D) cell culture technologies, which more closely mimic the complex microenvironment of tissue, are being increasingly evaluated as a tool for the preclinical screening of clinically promising new molecules, and studying of tissue metabolism. Studies of metabolites released into the extracellular space (secretome) allow understanding the metabolic dynamics of tissues and changes caused by therapeutic interventions. Although quite advanced in the field of proteomics, studies on the secretome of low molecular weight metabolites (< 1500 Da) are still very scarce. We present an untargeted metabolomic protocol based on the hybrid technique of liquid chromatography coupled with high-resolution mass spectrometry for the analysis of low-molecular-weight metabolites released into the culture medium by 3D cultures and co-culture (secretome model). For that we analyzed HT-29 human colon carcinoma cells and 3T3-L1 preadipocytes in 3D-monoculture and 3D-co-culture. The putative identification of the metabolites indicated a sort of metabolites, among them arachidonic acid, glyceric acid, docosapentaenoic acid and beta-Alanine which are related to cancer and obesity. This protocol represents a possibility to list metabolites released in the extracellular environment in a comprehensive and untargeted manner, opening the way for the generation of metabolic hypotheses that will certainly contribute to the understanding of tissue metabolism, tissue-tissue interactions, and metabolic responses to the most varied interventions. Moreover, it brings the potential to determine novel pathways and accurately identify biomarkers in cancer and other diseases. The metabolites indicated in our study have a close relationship with the tumor microenvironment in accordance with the literature review.

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.

TRAIL/S-layer/graphene quantum dot nanohybrid enhanced stability and anticancer activity of TRAIL on colon cancer cells

Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL), known as a cytokine of the TNF superfamily, is considered a promising antitumor agent due to its ability to selectively induce apoptosis in a wide variety of cancer cells. However, failure of its successful translation into clinic has led to development of nano-based platforms aiming to improve TRAIL therapeutic efficacy. In this regard, we fabricated a novel TRAIL-S-layer fusion protein (S-TRAIL) conjugated with graphene quantum dots (GQDs) to benefit both the self-assembly of S-layer proteins, which leads to elevated TRAIL functional stability, and unique optical properties of GQDs. Noncovalent conjugation of biocompatible GQDs and soluble fusion protein was verified via UV–visible and fluorescence spectroscopy, size and ζ-potential measurements and transmission electron microscopy. The potential anticancer efficacy of the nanohybrid system on intrinsically resistant cells to TRAIL (HT-29 human colon carcinoma cells) was investigated by MTT assay and flow cytometry, which indicated about 80% apoptosis in cancer cells. These results highlight the potential of TRAIL as a therapeutic protein that can be extensively improved by taking advantage of nanotechnology and introduce S-TRAIL/GQD complex as a promising nanohybrid system in cancer treatment.

IGF-1R depletion sensitizes colon cancer cell lines to radiotherapy.

Insulin like growth factor receptor 1 (IGF-1R) has been documented to play a key role in radiation response, thereby offering an attractive drug target to enhance tumor sensitivity to radiotherapy. Here, we investigated wether knockdown of IGF-1R can sensitize colorectal cancer (CRC) cell lines to radiation. Human colon carcinoma SW480 and HT-29 cells were transfected with specific small interference RNA (siRNA) to mediate IGF-1R depletion. The expression of IGF-1R mRNA and protein among transfected and untransfected cells was detected by Western blot analysis. Changes in cell proliferation and radiosensitivity were evaluated by the clonogenic survival assay. NVP-ADW742, an IGF-1R inhibitor, in combination with radiation was studied. RAD51, a measure for homologous recombination repair, and 53BP1, a maker for non-homologous end-joining (NHEJ), were determined by immunofluorescence for double-strand breaks (DSB) repair pathways. Cell cycle was also examined in the IGF-1R knockdown and IGF-1R-inhibited cells. CRC cell lines were selectively sensitized to radiation after siRNA-mediated IGF-1R depletion. NVP-ADW742 efficiently increases cancer cell response to radiation. Furthermore, initial formation of RAD51 foci after IR, and 53BP1 foci were significantly reduced in IGF-1R-depleted or with IGF-1R Inhibitor CRC cell lines. Lastly, IGF-1R-depleted or with IGF-1R Inhibitor caused more G2 phase cell arrest. Our findings demonstrate that depletion of IGF-1R lead to an increase in radiosensitivity in CRC.

Characterization of Oligomeric Proanthocyanidin-Enriched Fractions from Aronia melanocarpa (Michx.) Elliott via High-Resolution Mass Spectrometry and Investigations on Their Inhibitory Potential on Human Topoisomerases.

Aronia melanocarpa (MICHX.) ELLIOTT, which belongs to the Rosaceae family, has increasingly come into focus of research due to the high content of polyphenols. In addition to antioxidative properties, further health-promoting effects of these polyphenols are still of interest. Especially, the proanthocyanidins offer thereby huge opportunities due to their high structural heterogeneity. Therefore, the present study focuses on the topoisomerase inhibiting effects of oligomeric proanthocyanidins (PACs), which are potentially depended on their degree of polymerization. The investigated PACs isolated from Aronia berries were characterized by chromatographic techniques and liquid chromatography-high-resolution mass spectrometry. Four PAC enriched fractions were obtained from Aronia pomace containing 47 PACs with a degree of polymerization from three to six. Due to the low yield of hexamers, the potential inhibiting effects against human topoisomerase were investigated for the trimer to pentamer fractions. The relaxation and decatenation assays were performed to examine the inhibiting effect on topoisomerases under cell-free conditions. Moreover, rapid isolation of topoisomerase cleavage complexes in human colon carcinoma HT29 cells was performed to evaluate the effect on topoisomerases in a cell-based system. The fractions demonstrated inhibitory potential on topoisomerases I and II. In sum, an increasing effect strength depending on the degree of polymerization was shown.

Insight into the Web of Stress Responses Triggered at Gene Expression Level by Porphyrin-PDT in HT29 Human Colon Carcinoma Cells

Photodynamic therapy (PDT), a highly targeted therapy with acceptable side effects, has emerged as a promising therapeutic option in oncologic pathology. One of the issues that needs to be addressed is related to the complex network of cellular responses developed by tumor cells in response to PDT. In this context, this study aims to characterize in vitro the stressors and the corresponding cellular responses triggered by PDT in the human colon carcinoma HT29 cell line, using a new asymmetric porphyrin derivative (P2.2) as a photosensitizer. Besides investigating the ability of P2.2-PDT to reduce the number of viable tumor cells at various P2.2 concentrations and fluences of the activating light, we assessed, using qRT-PCR, the expression levels of 84 genes critically involved in the stress response of PDT-treated cells. Results showed a fluence-dependent decrease of viable tumor cells at 24 h post-PDT, with few cells that seem to escape from PDT. We highlighted following P2.2-PDT the concomitant activation of particular cellular responses to oxidative stress, hypoxia, DNA damage and unfolded protein responses and inflammation. A web of inter-connected stressors was induced by P2.2-PDT, which underlies cell death but also elicits protective mechanisms that may delay tumor cell death or even defend these cells against the deleterious effects of PDT.

Cytotoxic and apoptotic activity of Canavalia seed extract in HT-29 human colon carcinoma cells

Introduction and Aim: Concanavalin the lectin from Canavalia spp. share high structural similarity among the same taxon and exhibit wide range of biological functions. The antiproliferative activity of lectins ConA (C. ensiformis), ConC (C. cathartica), ConG (C. gladiata) and ConM (C. rosea) were studied in human colon carcinoma. &#x0D; &#x0D; Materials and Methods: Human colon carcinoma HT-29 cells and human normal kidney HEK293T cells were examined. The cytotoxicity was evaluated by MTT assay. Cell apoptosis was analyzed by AO-EB (acridine orange-ethidium bromide dual staining) method. Cell cycle was investigated by flow cytometry (RNase-propidium iodide-based flow cytometry). The expression of cell signaling genes was analyzed by qRT-PCR.&#x0D; &#x0D; Results: All concanavalins significantly inhibited the proliferation of HT-29 cells in dose-dependent manner (IC50 values were ConG-10.45, ConA-14.86, ConC-33.34 and ConM-48.98 µg/mL respectively). ConA and ConG induced apoptotic morphology in HT-29 cells without affecting HEK293T cells. Similarly, both lectins increased the sub-G0/G1 proportions in HT-29 cells dose-dependently. ConG showed down-regulation of AKT1, ERK1/2 and mutant p53 in HT-29 cells. &#x0D; &#x0D; Conclusion: Concanavalin extract is shown to possess cytotoxic effect through inducing apoptosis, especially causing cell cycle arrest at G0/G1 phase in HT-29 cells.

Topoisomerase poisoning by the flavonoid nevadensin triggers DNA damage and apoptosis in human colon carcinoma HT29 cells

Nevadensin, an abundant polyphenol of basil, is reported to reduce alkenylbenzene DNA adduct formation. Furthermore, it has a wide spectrum of further pharmacological properties. The presented study focuses the impact of nevadensin on topoisomerases (TOPO) in vitro. Considering the DNA-intercalating properties of flavonoids, first, minor groove binding properties (IC50 = 31.63 µM), as well as DNA intercalation (IC50 = 296.91 µM) of nevadensin, was found. To determine potential in vitro effects on TOPO I and TOPO IIα, the relaxation and decatenation assay was performed in a concentration range of 1–500 µM nevadensin. A partial inhibition was detected for TOPO I at concentrations ≥ 100 µM, whereas TOPO IIα activity is only inhibited at concentrations ≥ 250 µM. To clarify the mode of action, the isolating in vivo complex of enzyme assay was carried out using human colon carcinoma HT29 cells. After 1 h of incubation, the amount of TOPO I linked to DNA was significantly increased by nevadensin (500 µM), why nevadensin was characterized as TOPO I poison. However, no effects on TOPO IIα were detected in the cellular test system. As a subsequent cellular response to TOPO I poisoning, a highly significant increase of DNA damage after 2 h and a decrease of cell viability after 48 h at the same concentration range were found. Furthermore, after 24 h of incubation a G2/M arrest was observed at concentrations ≥ 100 µM by flow cytometry. The analysis of cell death revealed that nevadensin induces the intrinsic apoptotic pathway via activation of caspase-9 and caspase-3. The results suggest that cell cycle disruption and apoptotic events play key roles in the cellular response to TOPO I poisoning caused by nevadensin in HT29 cells.

Detection of subcellular nitric oxide in mitochondria using a pyrylium probe: assays in cell cultures and peripheral blood.

Fluorescent probes for the detection of intracellular nitric oxide (NO) are abundant, but those targeted to the mitochondria are scarce. Among those molecules targeting mitochondrial NO (mNO), the majority use a triphenylphosphonium (TPP) cation as a vector to reach such organelles. Here we describe a simple molecule (mtNOpy) based on the pyrylium structure, made in a few synthetic steps, capable of detecting selectively NO (aerated medium) over other reactive species. The calculated detection limit for mtNOpy is 88 nM. The main novelty of this probe is that it has a simple molecular architecture and can act both as a fluorogenic and as a mitochondriotropic agent, without using TPP. mtNOpy has been tested in two different scenarios: (a) in a controlled environment of cell line cultures (human colon carcinoma HT-29 cells and mouse macrophage RAW 264.7 cells), using confocal laser scanning microscopy, and (b) on a much more complex sample of peripheral blood, using flow cytometry. In the first context, mtNOpy has been found to be responsive (turn-on fluorescence) to exogenous and endogenous NO stimuli (via SNAP donor and LPS stimulation, respectively). In the second area, mtNOpy has been able to discriminate between NO-generating phagocytes (neutrophils and monocytes) from other leukocytes (NK, B and T cells).

Design, synthesis and evaluation of calix[4]arene-based carbonyl amide derivatives with antitumor activities.

Calixarenes, with potential functionalization on the upper and lower rim, have been explored in recent years for the design and construction of anticancer agents in the field of drugs and pharmaceuticals. Herein, optimization of bis [N-(2-hydroxyethyl) aminocarbonylmethoxyl substituted calix [4] arene (CLX-4) using structure-based drug design and traditional medicinal chemistry led to the discovery of series of calix [4]arene carbonyl amide derivatives 5a-5t. Evaluation of the cytotoxicity of 5a-5t employing MTT assay in MCF-7, MDA-MB-231 (human breast cancer cells), HT29 (human colon carcinoma cells), HepG2 (human hepatocellular carcinoma cells), A549 (human lung adenocarcinoma cells) and HUVEC (Human Umbilical Vein Endothelial) cells demonstrated that the most promising compound 5h displayed the most superior inhibitory effect against A549 and MDA-MB-231cells, which were 3.2 times and 6.8 times of CLX-4, respectively. In addition, the cell inhibition rate (at 10μM) against normal HUVEC cells invitro was only 9.6%, indicating the safty of compound 5h. Moreover, compound 5h could inhibit the migration of MDA-MB-231cell in wound healing assay. Further mechanism studies significantly indicated that compound 5h could block MDA-MB-231cell cycle arrest in G0/G1 phase by down regulating cyclin D1 and CDK4, and induce apoptosis by up-regulation of Bax, down-regulation of Caspase-3, PARP and Bcl-2 proteins, resulting in the reduction of DNA synthesis and cell division arrest. This work provides worthy of further exploration for the promising calixarene-based anticancer drugs.

Kimchi markedly induces apoptosis in HT-29 human colon carcinoma cells.

This study investigated kimchi-induced apoptosis in HT-29 human colon carcinoma cells. Three types of kimchi samples were prepared: standardized kimchi brined with general commercial Baechu cabbage by a standardized recipe (SK), Amtak Baechu kimchi brined with Amtak Baechu cabbage by a standardized recipe (AmK), and anticancer kimchi brined with organically cultivated Baechu cabbage by a functional recipe (AK). MTT assay, qRT-PCR, and Western blotting analysis were performed. The results indicate that AmK and AK, especially AK significantly upregulated mRNA expression of apoptosis-related genes Bim, Bax, Bak, caspase-8, -9, -3, and p53 but suppressed Bcl-xL and Bcl-2 expression. In addition, AK treatment significantly upregulated protein expression levels of caspase-3 but strikingly reduced the protein expression level of Bcl-2 (p<.05), followed by AmK treatment. Our data suggest that AK and AmK can markedly suppress the proliferation of HT-29 cells via activation of apoptosis. PRACTICAL APPLICATIONS: Colon cancer is the fourth cancer with the highest incidence in the world. Cell apoptosis is a type of programmed cell death and plays an important role in the cancer cells study. Kimchi is a traditional fermented food in Korea, with a relatively high daily consumption. Our present study used three kinds of kimchi which prepared with different main ingredients and recipes. The results suggest that organically cultivated Baechu cabbage and functional recipe in kimchi preparation play an important role in the anticancer efficacy of kimchi, which has been shown to promote induction of apoptosis in HT-29 cells.

Preclinical Evaluation of NHS-Activated Gold Nanoparticles Functionalized with Bombesin or Neurotensin-Like Peptides for Targeting Colon and Prostate Tumours.

Recent advances and large-scale use of hybrid imaging modalities like PET-CT have led to the necessity of improving nano-drug carriers that can facilitate both functional and metabolic screening in nuclear medicine applications. In this study, we focused on the evaluation of four potential imaging nanoparticle structures labelled with the 68Ga positron emitter. For this purpose, we functionalized NHS-activated PEG-gold nanoparticles with 68Ga-DOTA-Neuromedin B, 68Ga-DOTA-PEG(4)-BBN(7-14), 68Ga-DOTA-NT and 68Ga-DOTA-Neuromedin N. In vitro binding kinetics and specific binding to human HT-29 colon carcinoma cells and DU-145 prostate carcinoma cells respectively were assessed, over 75% retention being obtained in the case of 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP in prostate tumour cells and over 50% in colon carcinoma cells. Biodistribution in NU/J mice highlighted a three-fold uptake increase in tumours at 30 min post-injection of 68Ga-DOTA-NT-AuNP and 68Ga-DOTA-PEG(4)-BBN(7-14)-AuNP compared to 68Ga-DOTA-NT and 68Ga-DOTA-PEG(4)-BBN(7-14) respectively, therewith fast distribution in prostate and colon tumours and minimum accumulation in non-targeted tissues.

In Vitro Evaluation of Anti-Colon Cancer Potential of Crude Extracts of Fucoidan Obtained from Sargassum Glaucescens Pretreated by Compressional-Puffing

Fucoidans constitute a family of fucose-rich sulfated polysaccharides, which possess multiple characteristics, including antioxidant, antitumor, antivirus, anticoagulant, and anti-inflammatory properties. In addition, the incidence of colon cancer has risen rapidly worldwide. In the present study, fucoidan extracts were extracted from the Sargassum glaucescens (SG) pretreated by compressional-puffing, and four fucoidans (SG1-SG4) were obtained with different puffing conditions. It was found that SG4 possessed the highest extraction yield, relatively high cytotoxicity against human colon carcinoma HT-29 cells, and relatively low cytotoxicity to normal cells, as compared to the other extracted fucoidans. Moreover, SG4 caused cell cycle arrest of HT-29 cells at sub-G1, S, and G2/M phases. SG4 also induced HT-29 cellular apoptosis, as evidenced by the loss of mitochondrial membrane potential (MMP), increased cytochrome c release, activation of caspase-9 and -3, increased DNA fragmentation, and increased early and late apoptotic cells visualized by annexin V/propidium iodide (PI) assay. Additional biological experiments revealed that the Akt/mammalian target of rapamycin (mTOR)/S6 pathway is involved in SG4-induced apoptosis of HT-29 cells. These results clearly indicate that SG4 showed anti-colon cancer potential via the induction of cell cycle arrest and apoptosis, and thus may have a possible application as an adjuvant therapeutic agent in colon cancer treatment.

Trichothecenes from an Endophytic Fungus Alternaria sp. sb23.

Three new (alterchothecenes A - C, 1: -3: ) and 3 known (4: -6: ) trichothecenes, along with 9 known compounds (7: -15: ), were isolated from the culture of Alternaria sp. sb23, an endophytic fungus separated from the root of Schisandra sphenanthera Rehd. et Wils. Their structures were elucidated by spectroscopic analyses, and the absolute configurations of 1: -3: were determined through comparison of the experimental electronic circular dichroism (ECD) spectra and optical rotations with similar analogues. In vitro cytotoxicity tests of compounds 1: -6: against human HT-29 colon carcinoma and human MCF-7 breast cancer cell lines indicated that 4: -6: exhibited significant cytotoxic effects, with IC50 values ranging from 0.89 to 9.38 µM. And the potential of compounds 1: -6: as tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) sensitizers in HT-29 cells was evaluated. The results revealed that combination treatment of TRAIL with compounds 1: -6: synergistically decreased cell viability compared with the sole treatment with those compounds.

Lower Mg and S contents in solar salt used in kimchi enhances the taste and anticancer effects on HT-29 colon carcinoma cells

The anticancer effects of kimchi prepared with different kinds of solar salts were evaluated in an in vitro cellular system using HT-29 human colon carcinoma cells. Four kinds of kimchi samples were prepared, using different solar salts: conventionally manufactured solar salt (CS), filtered sea water solar salt (FS), dehydrated solar salt by centrifuging (DS), and washed-dehydrated solar salt (WDS). Prepared kimchi samples were presented as CSK, FSK, DSK, and WDSK, respectively. The pH values, acidity, and sensory evaluation were determined after 3 week fermentation at 5 °C (pH 4.3), and WDSK exhibited the best fermented characteristics and taste among the 4 samples examined. In the HT-29 cell growth inhibitory activity assay, all 4 kimchi samples exert dose-dependent cell growth inhibition, with WDSK showing significant growth inhibition of HT-29 cells. mRNA and protein expression levels of apoptosis and cell cycle arrest related factors reveals that WDSK significantly increases the mRNA expression levels of Bax, Bim, caspases-3, caspases-9, and p21 as compared to other kimchi samples, at a concentration of 4.0 mg mL−1. In addition, WDSK treatment strongly decreases the Bcl-2 protein expression (on western blot) in HT-29 cells, as compared to the control group (no kimchi treatment) and significantly increases the protein expression levels of Bax, caspases-3, caspases-9, and p53. Inductively coupled plasma atomic emission spectrometry (ICP-OES) reveals that WDS possesses a different mineral composition when compared to the other three solar salts; notably, the lower Mg (9.3 g kg−1) and S (4.7 g kg−1) content of WDS may cause better taste, fermented characteristcs, and functionality of WDSK. These results indicate WDS to be the ideal solar salt for kimchi preparation, which enhances the taste due to its lower Mg and S contents, and increases the anticancer effects by exerting better pro-apoptosis and cell cycle arrest abilities in HT-29 cells.

Transition metal complexes of α-aminophosphonates part II: Synthesis, spectroscopic characterization, and in vitro anticancer activity of copper(II) complexes of α-aminophosphonates

A one pot procedure was used to synthesize two new derivatives of α-aminophosphonates. Novel copper(II) complexes of α-aminophosphonates were synthesized by coordinating different copper salts with the newly synthesized α-aminophosphonates. Their structures were characterized by different spectral and analytical techniques. Evaluation of the metal-free ligands HL1, HL2, and their Cu(II) complexes against human colon carcinoma HT-29 cell lines was performed, using cisplatin as a reference drug. The results indicated that the complexes of the ligand HL1 exhibited enhanced anticancer activity, while ligand HL2 complexes showed decreased anticancer activity.

In Vivo Tumor Growth Inhibition and Antiangiogenic Effect of Cyclic NGR Peptide-Daunorubicin Conjugates Developed for Targeted Drug Delivery

Among various homing devices, peptides containing the NGR tripeptide sequence represent a promising approach to selectively recognize CD13 receptor isoforms on the surface of tumor cells. They have been successfully used for the delivery of various chemotherapeutic drugs to tumor vessels. Here, we report on the murine plasma stability, in vitro and in vivo antitumor activity of our recently described bioconjugates containing daunorubicin as payload. Furthermore, CD13 expression of KS Kaposi’s Sarcoma cell line and HT-29 human colon carcinoma cell line was investigated. Flow cytometry studies confirm the fast cellular uptake resulting in the rapid delivery of the active metabolite Dau = Aoa-Gly-OH to tumor cells. The increased in vitro antitumor effect might be explained by the faster rearrangement from NGR to isoDGR in case of conjugate 2 (Dau = Aoa-GFLGK(c[NleNGRE]-GG)-NH2) in comparison with conjugate 1 (Dau = Aoa-GFLGK(c[KNGRE]-GG)-NH2). Nevertheless, results indicated that both conjugates showed significant effect on inhibition of proliferation in the primary tumor and also on blood vessel formation making them a potential candidate for targeting angiogenesis processes in tumors where CD13 and integrins are involved.

Synthesis, Anti-proliferative Evaluation, and Molecular Docking Studies of 3-(alkylthio)-5,6-diaryl-1,2,4-triazines as Tubulin Polymerization Inhibitors

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.