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Nanotechnology-based targeting drug delivery systems have a considerable potential in medicine. Therefore, the present study aimed to designe, synthesise and characterize a nanodrug with beta lactoglobulin coating including oxali-palladium with and without folate and to compare their anti-cancer effects. The physicochemical properties of nanocapsules were studied by Dynamic light scattering (DLS), atomic force microscopy (AFM) and scanning electron microscopy (SEM). Finally, the anticancer activities of nanodrugs were investigated against human colorectal cancer cell line of HCT116 by MTT and flowcytometry methods. The results of Dynamic light scattering (DLS), scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that the average size of nanocapsules with folate were less than 40 nm. Cytotoxicity results proved the dose- and time-dependent antiproliferation and anicancer activities of nanocapsules (with folate) against HCT116. Finally, it could be concluded that folate increase anticancer activity of nanodrugs and it might be considered as a new candidate in the design and synthesis of new drugs in cancer treatment.

Background: The aim of the study is to determine the anticancer activity of Thymus algeriensis (TS) and its underlying mechanisms using in vitro and in animal models. Methods: HCT116 cells were treated with TS essential oil alone or with TRAIL, and then its anticancer effect was determined by using MTT assay, live dead assay, caspase activation and PARP cleavage. Further mechanisms of its anticancer effects was determined by analyzing expression of death receptor signaling pathway using Western blotting. A mouse model was also used to assess the antitumor potential of thyme essential oil. Results: TS oily fraction showed tumor growth inhibitory effect even at lower concentration. TS induces apoptotic cell death as indicated by cleavage of PARP, and activation of the initiator and effector caspases (caspase-3, -8 and -9). Further, results showed that TS increases the expression of death receptors (DRs) and reduces the expression of TRAIL decoy receptors (DcRs). In addition, upregulation of signaling molecules of MAPK pathway (p38 kinase, ERK, JNK), down-regulation of c-FLIP, and overexpression of SP1 and CHOP were observed by TS. Further in animal model, intragastric administration of TS (12.5 mg/ml and 50 mg/ml) prevented colorectal carcinogenesis by blocking multi-steps in carcinoma. Conclusion: Overall, these results indicate that thymus essential oil promotes apoptosis in HCT116 cells and impedes tumorigenesis in animal model. Moreover, thyme potentiates TRAIL-induced cell death through upregulation of DRs, CHOP and SP1 as well as downregulation of antiapoptotic proteins in HCT116 cells. However, therapeutic potential of TS needs to be further explored.

Background N-Alkylamides (NAAs), derived from Anacyclus pyrethrum (L.) DC, have potential anti-tumor effects. To explore the molecular mechanism and chemo-preventive capacity of NAAs, we synthesized an NAA (H-10) and evaluated whether it could inhibit the proliferation of B16, HepG2, HeLa, and HCT116 cancer cells in 2D culture. Methods To evaluate the antiproliferative activity of H-10 in 2D and 3D culture of BD, HepG2, HeLa, and HCT116 cells, multicellular tumor spheroids were constructed to more accurately reflect the cell tumor environment. To visualize nuclear changes related to apoptosis, Hoechst 33258 staining and propidium iodide-Annexin V double staining were performed. Results Compound H-10 strongly inhibited the growth of all tested cell lines. Hoechst 33258 staining and propidium iodide-Annexin V double staining revealed that H-10 did not cause morphological alterations in the nuclei and moderately induced late apoptosis only when treated at 180 μM. The strongest inhibitory effect was observed in HCT116 cells. Flow cytometry analysis indicated that treatment of HCT116 cells with compound H-10 resulted in robust cell growth arrest in G2 phase in 2D and 3D cell culture; in 3D-cultured HCT116 cells, growth arrest occurred in G1 phase. Treatment with compound H-10 also significantly suppressed angiogenesis of chick chorioallantoic membrane in vivo. Conclusion Treatment with compound H-10 strongly affected clonogenic survival (in the long-term) and migration of HCT116 cells. Therefore, H-10, a compound of NAAs may be useful for treating cancer because of its anti-neoplastic effect and easy synthesis.

A small library of cage-like heterocyclic hybrids encompassing pyrroloisoquinolines, pyridinone and acenaphthene structural moieties have been synthesized and tested for their potential as anticancer agents against HCT116 and JURKAT cell lines. The results revealed that these cell lines are more sensitive towards compound 1g and it showed dose dependent cytotoxic effect at 48 hrs of incubation. The IC50 values of compound 1g against HCT116 and JURKAT cell lines are 12.14 ± 1.53 and 10.68 ± 0.68 µM, respectively. Further studies on the determination of mechanism of action of compound 1g discovered that it brought the cell death by inducing Caspase 3 dependent apoptosis and also by arresting the cell cycle at S phase. These studies revealed that compound 1g can be recommended as a potential anti-cancer agent.

Novel 3(2H)-pyridazinone derivatives were designed, synthesised in satisfactory yields and evaluated in different experimental assays to assess their preliminary toxicity in vivo and anti-proliferative effects against HCT116 cell lines in vitro. Artemia salina lethality test provided LC50 values >100 mu g/mL for all compounds. Successive assays revealed that some compounds were endowed with a promising anti-proliferative effect against HCT116 cells, alone or stimulated by serotonin as a pro-inflammatory factor in order to mimick an inflamed model in vivo of cancer cell microenvironment. Moreover, the kinurenic acid level after treatment with these newly synthesised compounds was monitored as a marker of anti-proliferation in colon carcinoma models. The IC50 values obtained for the best-in-class compounds were comparable to that of daunorubicin as a reference drug. Conversely, these compounds were not able to counteract the spontaneous migration of human cancer HCT116 cell line in the wound healing paradigm.

Background Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial–mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators. Methods We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays. Results We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells. Conclusion We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. One of its subtypes is associated with defective mismatch repair (dMMR) genes. Saffron has many potentially protective roles against colon malignancy. However, these roles in the context of dMMR tumors have not been explored. In this study, we aimed to investigate the effects of saffron and its constituents in CRC cell lines with dMMR. Methods: Saffron crude extracts and specific compounds (safranal and crocin) were used in the human colorectal cancer cell lines HCT116, HCT116+3 (inserted MLH1), HCT116+5 (inserted MSH3), and HCT116+3+5 (inserted MLH1 and MSH3). CDC25b, p-H2AX, TPDP1, and GAPDH were analyzed by Western blot. Proliferation and cytotoxicity were analyzed by MTT. The scratch wound assay was also performed. Results: Saffron crude extracts restricted (up to 70%) the proliferation in colon cells with deficient MMR (HCT116) compared to proficient MMR. The wound healing assay indicates that deficient MMR cells are doing better (up to 90%) than proficient MMR cells when treated with saffron. CDC25b and TDP1 downregulated (up to 20-fold) in proficient MMR cells compared to deficient MMR cells, while p.H2AX was significantly upregulated in both cell types, particularly at &gt, 10 mg/mL saffron in a concentration-dependent manner. The reduction in cellular proliferation was accompanied with upregulation of caspase 3 and 7. The major active saffron compounds, safranal and crocin reproduced most of the saffron crude extracts’ effects. Conclusions: Saffron’s anti-proliferative effect is significant in cells with deficient MMR. This novel effect may have therapeutic implications and benefits for MSI CRC patients who are generally not recommended for the 5-fluorouracil-based treatment.

In the present study, a series of 2-(4-(2-chloroacetyl)piperazin-1-yl)-N-(2-(4-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetamide derivatives was synthesized and its chemical structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were evaluated for their in vitro antimicrobial (tube dilution technique) and anticancer (MTT assay) activities along with molecular docking study by Schrodinger 2018-1, maestro v11.5. The antimicrobial results indicated that compounds 3, 8, 11 and 12 displayed the significant antimicrobial activity and comparable to the standards drugs (ciprofloxacin and fluconazole). The anticancer activity results indicated that compound 5 have good anticancer activity among the synthesized compounds but lower active than the standard drugs (5-fluorouracil and tomudex). Molecular docking study demonstrated that compounds 5 and 7 displayed the good docking score with better anticancer potency within the binding pocket and these compounds may be used as a lead for rational drug designing for the anticancer molecules.

Background and Aims: Since 1980's, several preclinical studies have been published on the anti-colorectal cancer activity of the nonsteroidal anti-inflammatory drug indomethacin. The direct anti-proliferative effect of indomethacin seems to occur via a variety of reported COX-independent mechanisms. Acemetacin is a glycolic acid ester derivative of indomethacin and contrary to indomethacin, there is not much published research on anti-cancer effects of acemetacin. Herein, we compared the in vitro anti-proliferative properties of indomethacin, acemetacin, and their tromethamine salts in HCT116 colon cancer cells. Methods: The tromethamine salts of indomethacin and acemetacin were synthesized and the structures were established by microanalysis, IR, 1H-NMR, 13C-NMR (APT) and 2D-NMR (HSQC and HMBC) spectrometry. Cell proliferation assays were performed using xCELLigence real-time cell analysis system. Results: Indomethacin exhibited profound inhibitory effects with IC50 values at low micromolar ranges. Acemetacin exhibited far lower cytotoxic activity as compared to that of indomethacin. Surprisingly, indomethacin-tromethamine salt was 2-fold and 4.4-fold more potent than indomethacin at 48 and 72 h, respectively, while maintaining its activity at 24 h. The tromethamine salt of acemetacin was more potent than acemetacin at 24 h and 48 h post-treatment. Conclusion: The anti-proliferative effect of indomethacin in HCT116 cells was found to be at low micro-molar levels. The esterification of indomethacin with glycolic acid caused a strong decrease in anti-proliferative effect. The salt formation caused a positive effect on the anti-proliferative activity of indomethacin and indomethacin-tromethamine salt may be a promising candidate for additional in vivo studies.

International audience; (R)-1,2-Diaminobicyclo[2.2.2]octane was used as a starting material for the preparation, in solution or in a ball mill, of a salen ligand. Five metal salen complexes were prepared in high yield and their cytotoxic activities were evaluated against the Human Colon cancer HCT116 cell lines. The original manganese salen complex displayed the highest activity with a potency 16 fold higher than that of cisplatin, demonstrating the benefit of the bridging backbone compared to other salen systems. An alternative preparation route for this complex by mechanochemistry was also performed.

ObjectiveTo investigate Acacia honey from different altitudes regarding total phenols and flavonoids, laser-induced fluorescence (LIF) spectra and anticancer activity against human cancer cell lines.MethodsAnticancer activity was investigated using sulforhodamine B cytotoxicity assays in the following human cancer cell lines: HCT116 (colon); MCF7 (breast), and HepG2 (liver). Total phenols and flavonoids were measured using spectrophotometric methods and LIF was used to differentiate between low and high-altitude honey.ResultsThe LIF spectra differed between low and high-altitude Acacia honey. High altitude Acacia honey was characterized by significantly lower total phenol content (81.47 ± 1.25 mg gallic acid equivalent [GAE]/100 g) and increased total flavonoids (10.63 ± 0.53 mg quercetin equivalent [QE]/100 g) versus low altitude Acacia honey (91.33 ± 0.96 mg GAE/100 g and 8.78 ± 0.23 mg QE/100 g, respectively). Low altitude Acacia honey displayed increased IC50values against HCT116 and MCF7 cells (264.17 ± 10.5 and 482.65 ± 20.3 µg/ml, respectively) versus high altitude Acacia honey (117.99 ± 12.7 and 189.82 ± 15.8 µg/ml, respectively).ConclusionsHigh altitude Acacia honey had significantly more effective anticancer activity against HCT116 and MCF7 cells compared with low altitude honey.

Pyrrolomycins (PMs) are polyhalogenated antibiotics known as powerful biologically active compounds, yet featuring high cytotoxicity. The present study reports the antibacterial and antitumoral properties of new chemically synthesized PMs, where the three positions of the pyrrolic nucleus were replaced by nitro groups, aiming to reduce their cytotoxicity while maintaining or even enhancing the biological activity. Indeed, the presence of the nitro substituent in diverse positions of the pyrrole determined an improvement of the minimal bactericidal concentration (MBC) against Gram-positive (i.e., Staphylococcus aureus) or -negative (i.e., Pseudomonas aeruginosa) pathogen strains as compared to the natural PM-C. Moreover, some new nitro-PMs were as active as or more than PM-C in inhibiting the proliferation of colon (HCT116) and breast (MCF 7) cancer cell lines and were less toxic towards normal epithelial (hTERT RPE-1) cells. Altogether, our findings contribute to increase the knowledge of the mode of action of these promising molecules and provide a basis for their rationale chemical or biological manipulation.

Bouea macrophylla is a tree widely grown throughout South East Asia. It is used in folk medicine for the treatment of various illnesses. The present study aimed to identify the chemical constituents and to test the antimicrobial and anticancer activities of an ethanol extract from B. macrophylla leaves. The extract exhibited excellent antibacterial properties against 9 out of 10 target microorganisms. including four Gram-negative bacteria (Escherichia coli, Shigella flexneri, Vibrio cholera, and Pseudomonas aeruginosa) and four Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes, Enterococcus faecalis, and Bacillus cereus), as well as a fungus (Candida albicans). In addition, the extract was also tested on HeLa and human colorectal carcinoma (HCT116) cells to evaluate its cytostatic effects. The ethanol extract was able to inhibit the proliferation of HeLa and HCT116 cells, showing IC50 = 24 &plusmn, 0.8 and 28 &plusmn, 0.9 &micro, g/mL, respectively, whereas the IC50 values of doxorubicin (standard) were 13.6 &plusmn, 1.3 and 15.8 &plusmn, 1.1 &micro, g/mL respectively. Also, we identified various bioactive compounds in the extract such as polyphenols, flavonoids, caryophyllene, phytol, and trans-geranylgeraniol by GC-MS, which could contribute to the extract&rsquo, s biological activities. Therefore, our findings strongly indicate that the constituents of the B. macrophylla ethanol extract could be active against the tested bacteria and fungi as well as cancer cells. Further investigation is needed to understand the mechanisms mediating the antimicrobial and anticancer effects and identify signaling pathways that could be targeted for therapeutic application.

Inflammation mediated by the innate immune system is an organism's protective mechanism against infectious environmental risk factors. It is also a driver of the pathogeneses of various human diseases, including cancer development and progression. Microalgae are increasingly being focused on as sources of bioactive molecules with therapeutic potential against various diseases. Furthermore, the antioxidant, anti-inflammatory, and anticancer potentials of microalgae and their secondary metabolites have been widely reported. However, the underlying mechanisms remain to be elucidated. Therefore, in this study, we investigated the molecular mechanisms underlying the anti-inflammatory and anticancer activities of the ethanol extract of the Antarctic freshwater microalga Micractinium sp. (ETMI) by several in vitro assays using RAW 264.7 macrophages and HCT116 human colon cancer cells. ETMI exerted its anti-inflammatory activity by modulating the main inflammatory indicators such as cyclooxygenase (COX)-2, interleukin (IL)-6, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and nitric oxide (NO) in a dose-dependent manner. In addition, ETMI exerted cytotoxic activity against HCT116 cells in a dose-dependent manner, leading to significantly reduced cancer cell proliferation. Further, it induced cell cycle arrest in the G1 phase through the regulation of hallmark genes of the G1/S phase transition, including CDKN1A, and cyclin-dependent kinase 4 and 6 (CDK4 and CDK6, respectively). At the transcriptional level, the expression of CDKN1A gradually increased in response to ETMI treatment while that of CDK4 and CDK6 decreased. Taken together, our findings suggest that the anti-inflammatory and anticancer activities of the Antarctic freshwater microalga, Micractinium sp., and ETMI may provide a new clue for understanding the molecular link between inflammation and cancer and that ETMI may be a potential anticancer agent for targeted therapy of colorectal cancer.

Preparation of a biologically active benzofuran derivative ethyl 2-(4-fluorophenyl)-5-hydroxy-6-nitro - benzofuran-3-carboxylate from commercially available starting materials 2- bromo-4-methoxy-phenol andpara- fluorophenylacetylene is described in four steps with good yields. The final compound and all the intermediates reported in the method were characterized by spectroscopic techniques. Finally, the target molecule and its methyl derivative were tested for their anticancer activity and were found to be 95.2μg/mL and 8.5μg/mL (IC 50) respectively against HCT 116 cell line.

International audience; 1,3-Di(benzyloxy)imidazol-2-ylidenes (or NOHCs) possess structures related to N-heterocyclic carbenes (NHCs), with potentially useful applications including the stabilization of metals. In order to prepare NOHC metal complexes, a multi-step synthesis involving mechanochemistry, and making use of ball-milling, was designed. A library of unprecedented NHOC metal complexes were tested for their cytotoxic activities against HCT116 colorectal cancer cell line. The tests demonstrated that the studied complexes displayed a similar activity, comparable with that one exhibited by the ligand. However, a remarkable activity was found in the case of silver complex 5 with an IC50 value of 0.75 μM, comparable to that of doxorubicin.

Background Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts. Method Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition. Result Overall, MP-HX extract exhibited the highest antioxidant potential, with IC50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC50 = 57.81 ± 3.49 μg/mL) and HCT116 (IC50 = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC50 = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also demonstrated by their ability to induce caspase-dependent apoptotic cell death in all of the cancer cell lines tested. Cell cycle analysis suggested that both the MP-HX and MP-EA extracts were able to disrupt the cell cycle in most of the cancer cell lines. Conclusions MP-HX and MP-EA extracts demonstrated notable antioxidant, anti-proliferative, apoptosis induction and cancer cell cycle inhibition activities. These findings reflect the promising potentials of MP to be a source of novel phytochemical(s) with health promoting benefits that are also valuable for nutraceutical industry and cancer therapy. Electronic supplementary material The online version of this article (doi:10.1186/s12906-017-1761-9) contains supplementary material, which is available to authorized users.

Epithelial to mesenchymal transition (EMT) is a multipurpose process involved in wound healing, development, and certain pathological processes, such as metastasis formation. The Tks4 scaffold protein has been implicated in cancer progression, however, its role in oncogenesis is not well defined. In this study, the function of Tks4 was investigated in HCT116 colon cancer cells by knocking the protein out using the CRISPR/Cas9 system. Surprisingly, the absence of Tks4 induced significant changes in cell morphology, motility, adhesion and expression, and localization of E-cadherin, which are all considered as hallmarks of EMT. In agreement with these findings, the marked appearance of fibronectin, a marker of the mesenchymal phenotype, was also observed in Tks4-KO cells. Analysis of the expression of well-known EMT transcription factors revealed that Snail2 was strongly overexpressed in cells lacking Tks4. Tks4-KO cells showed increased motility and decreased cell&ndash, cell attachment. Collagen matrix invasion assays demonstrated the abundance of invasive solitary cells. Finally, the reintroduction of Tks4 protein in the Tks4-KO cells restored the expression levels of relevant key transcription factors, suggesting that the Tks4 scaffold protein has a specific and novel role in EMT regulation and cancer progression.

The antiproliferative action of hispolon derivatives is stronger than that of related curcumin against several tumor cell lines. Hispolon size, smaller than curcumin, fits better than curcumin into the active site of HDAC6, an enzyme involved in deacetylation of lysine residues. HDACs are considered potential targets for tumor drug discovery and hydroxamates are known inhibitors of HDACs. One of them, SAHA (Vorinostat) is used in clinical studies. Investigations into possible mechanisms for hispolon derivatives active against the HCT116 colon tumor cell line are done after examining the structural results obtained from hispolon X-ray crystal structures as well as performing associated computational docking and Density Functional Theory techniques on HDAC6. These studies show preference for the HDAC6 active site by chelating the Zn center, in contrast with other ineffective hispolon derivatives, that establish only a single bond to the metal center. Structure activity relationships make clear that hydrogenation of the hispolon bridge also leads to single bond (non chelate) hispolon-Zn binding, and consistently nullifies the antiproliferative action against HCT116 tumor.

In the present study, we examined a hypothesis that dichloroacetate, a metabolic inhibitor, might efficiently potentiate the cytotoxic effect of salinomycin, an antibiotic ionophore, on two human colorectal cancer derived cell lines DLD-1 and HCT116. First, we performed a series of dose response experiments in the 2D cell culture by applying mono- and combination therapy and by using the Chou-Talalay method found that salinomycin in combination with dichloroacetate acted synergistically in both cell lines. Secondly, in order to recapitulate the in vivo tumor architecture, we tested various doses of these compounds, alone and in combination, in the 3D multicellular spheroid culture. The effect of combination of dichloracetate and salinomycin on multicellular spheroid size was stronger than the sum of both monotherapies, particularly in HCT116 cells. Further, we demonstrate that the synergistic effect of compounds may be related to the inhibitory effect of dichloroacetate on multidrug resistance proteins, and in contrast, it is not related to dichloroacetate-induced reduction of intracellular pH. Our findings indicate that the combination therapy of salinomycin and dichloroacetate could be an effective option for colorectal cancer treatment and provide the first mechanistic explanation of the synergistic action of these compounds.

The standardized 80% ethanolic extract of the leaves of Ocimum basilicum var. thyrsiflorum (L.) Benth., Lamiaceae, growing in KSA, exhibited a significant antioxidant activity compared to the ethyl acetate and butanol extracts, which was correlated to its higher phenolic and flavonoid contents. Chromatographic separation of the 80% ethanol extract resulted in the isolation of ten known compounds; cinnamic acid, gallic acid, methylgallate, ellagic acid, methyl ellagic acid, apigenin, luteolin, vitexin, isovitexin, and 3″-O-acetylvitexin. Compound 3″-O-acetylvitexin, a C-glycosylated derivative of apigenin, was isolated for the first time from genus Ocimum. The 80% ethanolic extract and 3″-O-acetylvitexin showed significant cytotoxic activities against the HCT116 human colon cancer cell line [IC50 values 22.3 ± 1.1 and 16.8 ± 2.0 μg/ml (35.4 μM), respectively]. Keywords: Ocimum basilicum, HCT116, Cytotoxic, Antioxidant, C-glycosylation, Apigenin derivative

Colorectal cancer (CRC) is the third leading cause of cancer-associated mortality worldwide. Genipin is a medicinal herb compound derived from the gardenia fruit, which has been reported to exhibit antitumor activity against several types of cancer. The aim of the present study was to investigate the antitumor effect of genipin on colon cancer and the underlying molecular mechanisms. Genipin significantly inhibited the viability of HCT116 and SW480 cells in vitro in a dose- and time-dependent manner. Additionally, genipin was able to significantly inhibit tumor growth in nude mice with xenografts of HCT116 and SW480 cells. The inhibition of tumor growth by genipin treatment was coupled with G0/G1 cell cycle arrest, apoptosis induction, increased reactive oxygen species damage and loss of mitochondrial membrane potential. Further investigation of genipin-treated HCT116 cells revealed that the expression of p53, Bax and cleaved caspase-3 in genipin-treated cells was increased compared with the vehicle control, whereas B-cell lymphoma-2 expression appeared to be lower in genipin-treated cells. Collectively, the findings of the present study indicate that genipin was able to decrease proliferation and promote apoptosis in colon cancer cells by inducing the p53/Bax-mediated signaling pathway. Therefore, genipin may be used as a novel therapeutic agent in the treatment of CRC.

International audience; We selected edible and inedible mushrooms growing in the Mediterranean area of France to screen their biological activity: Caloboletus calopus, Rubroboletus lupinus, R. pulchrotinctus, R. satanas, Gyroporus castaneus, Suillus luteus, and Omphalotus olearius. Mushrooms were sequentially extracted using cyclohexane, chloroform, ethanol, and water. The antiproliferative activity against the HCT116 colon adenocarcinoma cell line and the antioxidant properties (DPPH radical scavenging assay, Folin-Ciocalteu assay, and oxygen radical absorbance capacity) of the Boletales extracts were evaluated and compared. Among the 28 mushroom extracts evaluated, 11 presented antiproliferative activity against HCT116 cells. These activities were not linked to antioxidant capacity. Among the antioxidant extracts, most were aqueous extracts in the oxygen radical absorbance capacity assay, whereas the highest values on the Folin-Ciocalteu and DPPH assays were noted for chloroform, ethanol, or aqueous extracts, depending on the mushroom species. Further studies are necessary to identify bioactive compounds and to valorize the mushrooms—for edible species, directly as health foods, or, for inedible mushrooms, as ingredients in the pharmaceutical and food industries.

The pro-apoptotic and inhibitory effects of the aflavin-3,3′-digallate (TFDG), which is the typical pigment in black tea, have been demonstrated in many cancer cell lines. However, TFDG is not stable in general culture conditions. So, to what extent TFDG or which degradation products of TFDG play an antitumor role is still unclear. In this study, we evaluated the effect of different treatments of TFDG on HCT116 cells. Compared with the control, both TFDG and O-TFDG (the TFDG that was pre-incubated in an incubator at 37°C for 3 hbefore adding into 96-well plates) significantly inhibited HCT116 cell growth. However, pre-treated TFDG was far better than TFDG. The IC50 values of TFDG and O-TFDG-3 were 17.26 μM and 8.98 μM, respectively (the cells were treated by O-TFDG for only 3 h, after which the media were replaced by fresh media for another 69 h incubation). Cell-cycle analysis revealed that 20 μM of O-TFDG and O-TFDG-3 caused cell-cycle arrest at G2 phase in HCT116 cells. Western blot analysis also demonstrated that the anti-inflammatory effect of O-TFDG-3 is stronger than that of TFDG by decreasing COX-2 and iNOS. On the other hand, O-TFDG induced HCT116 cells apoptosis mainly by increasing the expression of p53, p21, and cleaved caspase-3. The current study demonstrated that O-TFDG had a higher inhibitory effect on HCT116 cells than TFDG, and sowe may inferfromthis that the degradation products of TFDG play a key role against tumors.

Background Pyrimidine molecules attracted organic chemists very much due to their biological and chemotherapeutic importance. Their related fused heterocycles are of interest as potential bioactive molecules so, we have designed and prepared a new class of 4,4′-(1,4-phenylene)bis(pyrimidin-2-amine) molecules and screened for their in vitro antibacterial, antifungal and cytotoxicity studies. Results The structures of synthesized bis-pyrimidine molecules were confirmed by physicochemical and spectral means. The synthesized compounds were further evaluated for their in vitro biological potentials i.e. antimicrobial activity using tube dilution method and anticancer activity against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B assay. Conclusions The biological study demonstrated that compounds s7, s8, s11, s14, s16, s17 and s18 have shown more promising antimicrobial activity with best MIC values than the cefadroxil (antibacterial) and fluconazole (antifungal) and compound s3 found to have better anticancer activity against human colorectal carcinoma (HCT116) cancer cell line.

International audience; Two novel cycloruthenated compounds, 2 and 3, derived from cycloruthenated 2-phenyl pyridine(Ru(PhPy)) have been synthesized by adding one equivalent of 2,20;60,200-terpyridine (terpy) to [Ru(2-C6H4-20-C5H4N-kC,N)(MeCN)4]PF6 in MeOH/MeCN (16:1) at reflux temperature as a mixture of 1:1 isomers. The structures of both compounds that were formed under kinetic and thermodynamic control respectively, differ by the position of the central pyridine unit of terpy that was found trans or cis to the C-Ru bond of the Ru(PhPy) unit for 2 and 3 respectively. Whereas 2 did not afford substitution reactions when treated with any ligand, the substitution by MeOH or H2O of the MeCN trans to C in 3 could be followed by UV-vis spectroscopy. Moreover, the reaction in MeOH between 3 and imidazoles afforded new cycloruthenated compounds, 6a and 6b whose cytotoxicities, together with that of 2 and 3, against HCT116 and AGS cancer cells were determined.

The artemisinin compounds, which are well-known for their potent therapeutic antimalarial activity, possess in vivo and in vitro antitumor effects. Although the anticancer effect of artemisinin compounds has been extensively reported, the precise mechanisms underlying its cytotoxicity remain under intensive study. In the present study, a high-throughput quantitative proteomics approach was applied to identify differentially expressed proteins of HCT116 colorectal cancer cell line with artesunate (ART) treatment. Through Ingenuity Pathway Analysis, we discovered that the top-ranked ART-regulated biological pathways are abrogation of fatty acid biosynthetic pathway and mitochondrial dysfunction. Subsequent assays showed that ART inhibits HCT116 cell proliferation through suppressing the fatty acid biosynthetic pathway and activating the mitochondrial apoptosis pathway. In addition, ART also regulates several proteins that are involved in NF-κB pathway, and our subsequent assays showed that ART suppresses the NF-κB pathway. These proteomic findings will contribute to improving our understanding of the underlying molecular mechanisms of ART for its therapeutic cytotoxic effect towards cancer cells.

The present study compared the effect of resveratrol on HCT116 and Caco-2 human colon cancer cells. Annexin V/propidium iodide staining, MTT assay and western blot analysis revealed that resveratrol induced cycle arrest in the two cell lines, which was evidenced by cell cycle analysis and changes in the expression of the cell cycle proteins cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, proliferating cell nuclear antigen and P21. Furthermore, resveratrol was found to have a strong apoptosis-inducing effect, which was evidenced through the high percentage of annexin V positive cells and high protein expression of cleaved-caspase-7, cleaved-caspase-9 and cleaved-poly(ADP-ribose) polymerase in the resveratrol-treated cancer cells. In conclusion, these results demonstrated that resveratrol had greater growth inhibitory and cell cycle arrest effects on Caco-2 cells than HCT116 cells, through caspase-dependent and cyclin-CDK pathways.

In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116). The processes, carried out under optimal conditions, were: (1) pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent) at lab-scale; (2) Single-step supercritical fluid extraction (SFE) at pilot scale; (3) Intensified two-step sequential SFE at pilot scale; (4) Integrated PLE plus supercritical antisolvent fractionation (SAF) at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight), this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA) and carnosol (CS) at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide), suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts., This work was supported by the projects AGL2014-53609-P (Ministerio de Economía y Competitividad, Spain) and S2013/ABI-2728 (Comunidad de Madrid)., We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

This paper reports the synthesis, characterisation and DFT analysis of an N,O bidentate Schiff base, (( E )-(4-methoxybenzylimino)methyl)phenol, (L1c) and its Ni(II) and Pd(II) complexes. The structures were elucidated via elemental analysis, UV–Visible, NMR, IR and single crystal X-ray diffraction. Complexation of L1c with Ni(II) and Pd(II) was observed to induce different degrees of bathochromic effect on n → π ∗ and π → π ∗ electronic transitions. A comparison of the experimental data of UV–Visible, NMR, IR and X-ray with those calculated using DFT and TD-DFT methods where five hybrid functionals were tested in gas, IEF-PCM and SS-PCM models was also carried out. The results show that the reproduction of maximum absorption bands n → π ∗ and π → π ∗ is strongly related to the tested hybrid functionals and solvatochromic effects. Relatively good concordance was obtained between experimental and calculated NMR chemical shifts, IR and X-ray parameters. A bioactivity evaluation against HCT116 and Escherichia coli displayed that the parent ligand L1c is a more superior anticancer and antibacterial agent than the positive controls of 5FU and gentamicin respectively. However, both complexes showed poor activity as anticancer agent and no activity observed against tested bacteria.

Background Colorectal cancer (CRC) is a leading cause of cancer death globally and new biomarkers and treatments are severely needed. Methods Here, we employed HCT116 and LoVo human CRC cells made resistant to either SN38 or oxaliplatin, to investigate whether altered expression of the high affinity glutamate transporters Solute Carrier (SLC)-1A1 and -1A3 (EAAT3, EAAT1) is associated with the resistant phenotypes. Analyses included real-time quantitative PCR, immunoblotting and immunofluorescence analyses, radioactive tracer flux measurements, and biochemical analyses of cell viability and glutathione content. Results were evaluated using one- and two-way ANOVA and Students two-tailed t-test, as relevant. Results In SN38-resistant HCT116 and LoVo cells, SLC1A1 expression was down-regulated ~60 % and up-regulated ~4-fold, respectively, at both mRNA and protein level, whereas SLC1A3 protein was undetectable. The changes in SLC1A1 expression were accompanied by parallel changes in DL-Threo-β-Benzyloxyaspartic acid (TBOA)-sensitive, UCPH101-insensitive [3H]-D-Aspartate uptake, consistent with increased activity of SLC1A1 (or other family members), yet not of SLC1A3. DL-TBOA co-treatment concentration-dependently augmented loss of cell viability induced by SN38, while strongly counteracting that induced by oxaliplatin, in both HCT116 and LoVo cells. This reflected neither altered expression of the oxaliplatin transporter Cu2+-transporter-1 (CTR1), nor changes in cellular reduced glutathione (GSH), although HCT116 cell resistance per se correlated with increased cellular GSH. DL-TBOA did not significantly alter cellular levels of p21, cleaved PARP-1, or phospho-Retinoblastoma protein, yet altered SLC1A1 subcellular localization, and reduced chemotherapy-induced p53 induction. Conclusions SLC1A1 expression and glutamate transporter activity are altered in SN38-resistant CRC cells. Importantly, the non-selective glutamate transporter inhibitor DL-TBOA reduces chemotherapy-induced p53 induction and augments CRC cell death induced by SN38, while attenuating that induced by oxaliplatin. These findings may point to novel treatment options in treatment-resistant CRC. Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1405-8) contains supplementary material, which is available to authorized users.

The mitochondrial redox state and its heterogeneity of colon cancer at tissue level have not been previously reported. Nor has how p53 regulates mitochondrial respiration been measured at (deep) tissue level, presumably due to the unavailability of the technology that has sufficient spatial resolution and tissue penetration depth. Our prior work demonstrated that the mitochondrial redox state and its intratumor heterogeneity is associated with cancer aggressiveness in human melanoma and breast cancer in mouse models, with the more metastatic tumors exhibiting localized regions of more oxidized redox state. Using the Chance redox scanner with an in-plane spatial resolution of 200 μm, we imaged the mitochondrial redox state of the wild-type p53 colon tumors (HCT116 p53 wt) and the p53-deleted colon tumors (HCT116 p53-/-) by collecting the fluorescence signals of nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins [Fp, including flavin adenine dinucleotide (FAD)] from the mouse xenografts snap-frozen at low temperature. Our results show that: (1) both tumor lines have significant degree of intratumor heterogeneity of the redox state, typically exhibiting a distinct bi-modal distribution that either correlates with the spatial core–rim pattern or the "hot/cold" oxidation-reduction patches; (2) the p53-/-group is significantly more heterogeneous in the mitochondrial redox state and has a more oxidized tumor core compared to the p53 wt group when the tumor sizes of the two groups are matched; (3) the tumor size dependence of the redox indices (such as Fp and Fp redox ratio) is significant in the p53-/-group with the larger ones being more oxidized and more heterogeneous in their redox state, particularly more oxidized in the tumor central regions; (4) the H&E staining images of tumor sections grossly correlate with the redox images. The present work is the first to reveal at the submillimeter scale the intratumor heterogeneity pattern of the mitochondrial redox state in colon cancer and the first to indicate that at tissue level the mitochondrial redox state is p53 dependent. The findings should assist in our understanding on colon cancer pathology and developing new imaging biomarkers for clinical applications.