Human Cancer Cell Line HCT116 Research Articles

Antimicrobial, Anticancer, and Antioxidant Activities of Maize and Clover Pollen Grains Extracts: A Comparative Study with Phytochemical Characterizations.

The failure to treat infectious diseases due to the continual emergence of drug-resistant microbes poses a huge and serious challenge for human health globally. Currently, the discovery and development of natural therapeutic compounds are attracting considerable attention from researchers worldwide. In this project, two types of pollen grains (maize and clover) were evaluated for potential antimicrobial activities. Extracts of both pollen grains were purified using HPLC, which has been shown to have numerous phenolic and flavonoid compounds. Pyro catechol and methyl gallate were detected in high concentrations (1145.56 and 1056.57 µg/mL, respectively) in the maize extract, while caffeic acid, quercetin, and kaempferol (464.73, 393.05, and 390.93 µg/mL, respectively) were among the compounds observed at high concentrations in the clover pollen grains extract. Staphylococcus aureus, Escherichia coli, Salmonella typhi, and Candida albicans were more sensitive to the clover pollen grains extract with inhibition zones of 22 ± 0.2, 18 ± 0.1, 29 ± 0.3, and 42 ± 0.4 mm compared to the size of the inhibitory zones caused by the maize pollen grains extract (19 ± 0.3, 15 ± 0.4, 27 ± 0.1, and 22 ± 0.4 mm, respectively). Moreover, lower MIC values for the clover pollen grains extract were recorded against C. albicans (1.97 ± 0.04 µg/mL), S. aureus (62.5 ± 1.00 µg/mL), and E. coli (62.5 ± 0.07 µg/mL) than the MICs caused by the maize pollen grains extract. The use of a transmission electron microscope revealed that the E. coli that had been treated with the clover pollen grains extract showed changes in its cell walls compared to that treated with the maize pollen grains extract. The clover pollen grains extract exhibited a stronger antioxidant potential, with an IC50 value of 22.18 µg/mL, compared to an IC50 value of 54.85 µg/mL for the maize pollen grains extract, via a DPPH scavenging assay. Regarding anticancer activity, the maize pollen grains extract was revealed to be more effective in terms of inhibiting the human colon cancer cell line HCT-116, with an IC50 value of 67.02 ± 1.37 µg/mL, compared with the observed toxicity caused by the clover extract, with an IC50 value of 75.03 ± 1.02 µg/mL. Overall, the clover pollen grains extract demonstrated potent antibacterial and antioxidant activities, but not anticancer activity, when compared to the maize grains extract. Thus, the current findings related to both types of pollen grains (clover and maize) highlight their potential therapeutic applications for the treatment of certain infectious diseases and malignancies.

MgO-ZnO nanoparticle as an efficient photocatalyst in the synthesis of substituted chromeno[4, 3-b]chromenes as effective drugs in gastrointestinal cancer therapy

Chromeno[4,3-b]chromenes are biologically active compounds that have many applications in medicine, especially, in gastrointestinal field because of their anti-inflammatory and antioxidant properties. In this study, an efficient and environmental benign photocatalyst MgO-ZnO is proposed for the synthesis of a range of substituted chromenes under irradiation of a common green laser. To characterize MgO-ZnO techniques such as FT-IR, DRS, XRD, and FE-SEM are employed to ascertain the structure and physicochemical properties of the nanomaterial. Furthermore, an in-vitro cellular toxicity test was achieved on HCT-116 human gastrointestinal cancer cell line by MTT assay.

An extract from the frass of swallowtail butterfly (Papilio machaon) larvae inhibits HCT116 colon cancer cell proliferation but not other cancer cell types

BackgroundThe frass of several herbivorous insect species has been utilised as natural medicines in Asia; however, the metabolite makeup and pharmaceutical activities of insect frass have yet to be investigated. Oligophagous Papilionidae insects utilise specific kinds of plants, and it has been suggested that the biochemicals from the plants may be metabolised by cytochrome P450 (CYP) in Papilionidae insects. In this study, we extracted the components of the frass of Papilio machaon larvae reared on Angelica keiskei, Oenanthe javanica or Foeniculum vulgare and examined the biological activity of each component. Then, we explored the expression of CYP genes in the midgut of P. machaon larvae and predicted the characteristics of their metabolic system.ResultsThe components that were extracted using hexane, chloroform or methanol were biochemically different between larval frass and the host plants on which the larvae had fed. Furthermore, a fraction obtained from the chloroform extract from frass of A. keiskei-fed larvae specifically inhibited the cell proliferation of the human colon cancer cell line HCT116, whereas fractions obtained from the chloroform extracts of O. javanica- or F. vulgare-fed larval frass did not affect HCT116 cell viability. The metabolites from the chloroform extract from frass of A. keiskei-fed larvae prevented cell proliferation and induced apoptosis in HCT116 cells. Next, we explored the metabolic enzyme candidates in A. keiskei-fed larvae by RNA-seq analysis. We found that the A. keiskei-fed larval midgut might have different characteristics from the O. javanica- or F. vulgare-fed larval metabolic systems, and we found that the CYP6B2 transcript was highly expressed in the A. keiskei-fed larval midgut.ConclusionsThese findings indicate that P. machaon metabolites might be useful as pharmaceutical agents against human colon cancer subtypes. Importantly, our findings show that it might be possible to use insect metabolic enzymes for the chemical structural conversion of plant-derived compounds with complex structures.

Bacterial amidohydrolases and modified 5-fluorocytidine compounds: Novel enzyme-prodrug pairs.

Gene-directed enzyme prodrug therapy is an emerging strategy for cancer treatment based on the delivery of a gene that encodes an enzyme that is able to convert a prodrug into a potent cytotoxin exclusively in target cancer cells. However, it is limited by the lack of suitable enzyme variants and a scarce choice of chemical bonds that could be activated. Therefore, this study is aimed to determine the capability of bacterial amidohydrolases YqfB and D8_RL to activate novel prodrugs and the effect such system has on the viability of eukaryotic cancer cells. We have established cancer cell lines that stably express the bacterial amidohydrolase genes and selected several N4-acylated cytidine derivatives as potential prodrugs. A significant decrease in the viability of HCT116 human colon cancer cell lines expressing either the YqfB or the D8_RL was observed after exposure to the novel prodrugs. The data we acquired suggests that bacterial YqfB and D8_RL amidohydrolases, together with the modified cytidine-based prodrugs, may serve as a promising enzyme-prodrug system for gene-directed enzyme prodrug therapy.

ZnO-ZnS Heterostructure as a Potent Photocatalyst in the Preparation of Some Substituted Chromenes and Remarkable Antigastrointestinal Cancer Activity.

The nanosized hybrid material ZnO-ZnS was synthesized using the well-known sol-gel method, as a simple and environmentally friendly procedure. The material was then characterized using various techniques including FESEM, TEM, UV-vis, DRS, EDS, XRD, and FT-IR. The characterization studies revealed the generation of ZnO-ZnS nanoparticles with a mean size of around 25 nm. Moreover, DRS analysis provided a band gap of 3.05 eV for this nanomaterial. The photocatalytic properties of the ZnO-ZnS heterojunction was investigated in the synthesis of some substituted chromenes under mild reaction conditions. The results showed that the prepared nanophotocatalyst exhibits significantly higher activity compared to its individual components (ZnO and ZnS) and provides 73-87% yield with 0.01 g of ZnO-ZnS after 30 min. In addition, the nanophotocatalyst demonstrated a high reusability in the desired condensation reaction. The enhanced photocatalytic activity of ZnO-ZnS can be attributed to the slower recombination of the electron-hole pairs in this semiconductor material. The reactive species OH•, •O2-, and h+ are believed to play important roles in the photocatalytic system. Furthermore, cellular toxicity of ZnO-ZnS nanoparticles was evaluated on HCT-116 human gastrointestinal cancer cell line by MTT assay. The results proved a distinct reduction of cell viability, proofing cytotoxicity of nanoparticles on the cancer cells. This study highlights the potential of the nanoparticles against gastrointestinal cancer.

Psoralea corylifolia formula extract-loaded silk fibroin/polycaprolactone fibrous membrane for the treatment of colorectal cancer

Intestinal obstructions caused by intestinal tumors pose life-threatening risks to patients. Adjuvant treatment using intestinal stents carrying drug loaded membranes has the advantages of timely relief of intestinal obstruction, as well as effective inhibition of tumor progression. The present work is to develop an intestinal stent loaded with a combination of traditional Chinese medicines capable of good biocompatibility, degradability, sustained drug release and anti-tumor properties. The drug combination extract was obtained from Psoralea corylifolia formula (PCF) and then was loaded into silk fibroin (SF)/polycaprolactone (PCL) fibrous membranes using emulsion electrospinning technology. Results showed that the membrane prepared by emulsion electrospinning technology has apparent core-shell structure, and the mechanical property and hydrophilicity of the membrane are gradually improved with the addition of PCF. Drug sustained release results demonstrated that there were no bursting phenomena, and showed a gradual sustained release up to 400 h. The antitumor efficacy was assessed in vitro using a human colorectal cancer cell line HCT-116 and an epithelial cell line NCM-460. Results showed that this drug-loaded membrane sustained antitumor cell growth performance, indicating its great potential for clinical treatment for intestinal cancer in the near future.

Induction of Apoptosis by Cynaropicrin in Human Colon Cancer Cell Line HCT-116 through the Mitochondria-mediated Apoptotic Pathway

Background Colon cancer continues to be the third most commonly occurring cancer around the globe with both lifestyle-related risk factors and genetic dispositions. Owing to the increased incidence of the disease, there is a need to find new treatment options which are easily accessible and less toxic to the cells. Cynaropicrin, a sesquiterpene extract from the artichoke plant exhibits varied properties such as anti-inflammatory, anti-cancer, and antioxidant among others. In the current investigation, the anti-cancer potential of the cynaropicrin extract was observed against colon cancer in HCT-116 cell lines. Materials and Methods The drug exhibited a considerable decrease in cell proliferation. Also analyzed was the reactive oxygen species (ROS) generation and apoptosis induction by cynaropicrin on the HCT-116 cell line. The AO/EtBr staining confirmed the apoptotic induction through chromatin condensation by fluorescence microscopic examination followed by DAPI staining of the treated HCT-116 cells which showed nuclear condensation and disintegration. Results Furthermore, it was observed that cynaropicrin elevated the levels of ROS in the cells which modified the mitochondrial membrane permeability in the HCT-116 cell lines. The study also evaluated the levels of apoptotic proteins and the expression of inflammatory cytokines concerning cells treated with cynaropicrin and untreated control cells. Conclusion It has been observed that cynaropicrin treatment can lead to apoptosis in the HCT-116 cell line via mitochondria-mediated apoptotic pathway and if further evaluated, it can turn out to be a potent anti-cancer drug for effective management of colon cancer.

WO3-ZnS Photocatalyzed Synthesis of Some Substituted Benzimidazoles as Effective Agents against Gastrointestinal Cancer

Benzimidazoles, a class of nitrogen-containing heteroaromatic compounds, play a crucial role in the development of various important drugs. These compounds exhibit diverse biological functionalities. In this study, a novel and environmentally friendly photocatalytic route is proposed for the production of benzimidazoles. This method involves the oxidation of alcohol to aldehyde using air as the oxidant under visible-light conditions. Subsequently, fast condensation with o-phenylenediamine takes place, leading to the formation of 2-substituted benzimidazoles. The key mediator in this process is a newly developed photocatalyst called WO3-ZnS, which is activated by a commercial green laser light with a wavelength of 535 nm. To characterize the nanocomposite, several techniques including FT-IR, XRD, EDS, and FE-SEM were employed. These analyses provided valuable insights into the structure and properties of the nanocomposite. Moreover, Tauc’s method was utilized to estimate the optical band gap of the photocatalyst. The proposed photocatalytic process involves a radical pathway including reactive species such as •O2 - and OH•, along with h+. Stability and reusability experiments confirmed the reproducibility of the nano-photocatalyst in the reaction medium. Furthermore, the primarily in-vitro cellular toxicity of WO3-ZnS nanoparticles was evaluated using the HCT-116 human cancer cell line through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The results demonstrated a significant reduction in cell viability, indicating the cytotoxicity of the nanoparticles against these cancerous cells. This finding highlights the potential of the synthesized nanoparticles as effective agents for combating gastrointestinal cancer.

A Network Pharmacology-based Mechanism of the Traditional Chinese Medicine Formula Li Kun Zhi Ji acting on Colon Cancer

Backgrounds: Li Kun Zhi Ji (LKZJ) is a traditional Chinese medicine formula that effectively improves the immune system. However, the mechanism of its action against cancer remains unknown. Our study aimed to determine whether LKZJ inhibits the growth of the human colon cancer cell line HCT-116, and we performed in vitro experiments to further explore the associated molecular mechanisms. Objective: We explored the antitumor function and the mechanism of LKZJ against human colon cancer cells. Methods: We selected the effective components of LKZJ. Then, the potential targets of these components were obtained against colon cancer, and an “LKZJ-targets-colon cancer” network was constructed. After that, a CCK-8 assay was used to assess cell viability. Next, apoptosis was analyzed with PI/Annexin V assay using flow cytometry. Finally, western blotting was carried out to determine the expression levels of the protein. Results: We obtained 36 effective LKZJ components and identified 225 candidate targets acting on colon cancer. We demonstrated that the cell viability of HCT-116 cells had significantly decreased after treatment of LKZJ. The suppression of HCT-116 proliferation by LKZJ through inducing apoptosis was determined using Flow cytometry. In addition, mitochondria-associated apoptosis was stimulated, and the down-regulation of Bcl-2 and up-regulation of Bax and Bad were observed. LKZJ also attenuated the PI3K/Akt signaling pathway through western blotting. Conclusion: Our study revealed that LKZJ induced HCT-116 cell line apoptosis through the PI3K/Akt apoptotic pathway. Our results indicated that LKZJ could be a possible therapeutic agent against human colon cancer.

Effect of 3, 4-Dihydroxyphenylethanol on Antioxidant Enzymes Activity and Malondialdehyde Level in HCT-116 Cell Line

Background: There is much evidence-based research on the anti-cancerous effect of antioxidants. Dihydroxyphenylethanol is a potent antioxidant that has several activities, such as oxidant stress control, cell proliferation inhibitory activity, and apoptosis induction. The present study aimed to evaluate the effect of dihydroxyphenylethanol on antioxidant enzyme activity and malondialdehyde level in the HCT-116 cell line. Materials and Methods: In this study, a human colorectal cancer cell line HCT-116 was treated with different concentrations of 3, 4-dihydroxyphenylethanol (50, 100, 150, and 200 μM) for 24 h. Then, the level of malondialdehyde and activity of enzymes of catalase, superoxide dismutase, and glutathione peroxidase were measured by colorimetric methods. Results: The results showed that 3,4-dihydroxyphenylethanol administration resulted in significant reduction of the malondialdehyde concentration and also significant increase of the antioxidant enzymes (e.g., catalase, superoxide dismutase, and glutathione peroxidase) in the treatment groups compared to the control group (P<0.05). Conclusion: Overall, 3, 4-dihydroxyphenylethanol may result in reduction of oxidative stress on HCT-116 line through changes in concentration of the malondialdehyde and antioxidant enzymes activity.

Principal component analysis of phenolic compounds of grape waste parts and correlations to their bioassays

Investigating the phytochemical composition and the biological activities of stems, seeds, and peels of grape, Vitis vinifera was achieved. HPLC/DAD analysis of the three crude extracts resulted in the identification and quantification of 21 phenolic acids and 16 flavonoids against authentic compounds. Principal component analysis (PCA) plots were performed to illustrate the variances among the three samples. The quantitative analysis revealed that stem extract contained the highest total phenolic (TP) and total flavonoid (TF) contents and exerted the highest antioxidant effect. Seed extract showed outstanding bactericidal and fungicidal effects against the tested microorganisms. It also demonstrated the highest cytotoxic action against human cancer cell lines MCF-7 and HCT-116, while peel extract was the most active against PC-3 and HEPG2. PCA allowed the discrimination between grape samples; peels could be positively associated with apigenin. Pearson's correlation analysis was carried out between TF and TP contents of the tested extracts and their biological activities. Correlation coefficient (r) showed a significant, strong positive correlation between DPPH scavenging power and TP, TF contents, while the cytotoxicity and antimicrobial activities were medium positive to negatively correlated to TP and TF contents. Moreover, biosafety studies for the extracts were carried out and proved the safety of all extracts, whereas LD50 was more than 5 g/kg b. wt. Additionally, serum biomarkers, body and organs weights did not show any deviation from the normal rat's scale. Genotoxicity and antimutagenicity assays proved that the examined grape extracts had the potential to reverse the genotoxicity of cyclophosphamide, an anticancer medication.

Metformin Induces a Caspase 3-Unrelated Apoptosis in Human Colorectal Cancer Cell Lines HCT116 and SW620.

To study the effects of metformin on the proliferation and growth of human colorectal cancer cell lines HCT116 and SW620. The antiproliferative effect of metformin was assayed using an MTS reagent and its ability to inhibit colony formation was demonstrated using a clonogenic assay. Flow cytometry using YO-PRO-1/PI was performed to examine the effects of metformin on apoptosis and cell death of HCT116 and SW620. Caspase 3 activities were measured in caspase-3 activity tests using a caspase-3 activity kit. Furthermore, Western blots were performed with anti-PARP1, anti-caspase 3, and anti-cleaved caspase 3 to confirm whether caspase activation was present or not. Both MTS proliferation assays and clonogenic assays showed that metformin inhibited the proliferation and growth of HCT116 and SW620 cells in a concentration-dependent manner. Flow cytometric analysis identified early apoptosis and metformin-induced cell death in both cell lines. However, caspase 3 activity could not be detected. Cleavage of both PARP1 and pro-caspase 3 was not observed in the Western blot, confirming the absence of caspase 3 activations. This present study suggests a caspase 3-unrelated apoptosis mechanism of metformin-induced cell death in human colorectal cancer cell lines HCT116 and SW620.

Oxaliplatin: an effective treatment in colorectal cancer

Colorectal cancer is one of the most common malignancies around the world. Oxaliplatin is a new platinum compoundwith promising activity in colorectal cancer treatment. Based on the analysis of preclinical data. Because Oxaliplatincan lead to ICD (Immunogenic cell death), the study aims to figure out whether increasing concentrations and treatmentdurations with Oxaliplatin can kill colorectal cancer cells to test whether Oxaliplatin has a significant effect on colorectalcancer treatment. Using the human colorectal cancer cell line HCT116, the cancer cells will be treated with Oxaliplatinand PBS (negative control) at concentrations 1 mM, 10 mM, or 100 mM in a dose-dependent and duration-dependentmanner (1,3,6,12,24 hours ). Measure killing in vitro with MTT assay and measure tumor size in vivo. Also, measureHMGB-1 released by western blot and CRT by FACS. The positive control is cisplatin, and the negative is PBS/DMSOfor in vitro and saline solution for in vivo. The study’s findings will supply insight into the latent capacity of Oxaliplatinas a treatment for colorectal cancer in the future.

CREATION OF ISOGENIC CELL LINE MODELS OF 17P DELETION TO STUDY CLONAL EVOLUTION AND MECHANISMS OF THERAPY RESISTANCE IN CLL AND DLBCL

Introduction: A deletion of chromosome 17p (del17p), on which the tumour suppressor gene TP53 is located, is a prevalent genetic aberration in many cancer types. In chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), and other B cell malignancies this chromosomal mutation is associated with high fitness advantage in the setting of therapy, and the most adverse clinical outcome. Whilst resistance to the chemoimmunotherapies often used in the treatment of CLL and DLBCL can be explained by the functional loss of p53, such deactivation does not explain the increase in aggressive behaviour of the malignant cells. To study this, we aimed to develop in-vitro models of 17p deletion in CLL and DLBCL by creating TP53 (15.6 kbp) and 17p (20.5 Mbp) deletions by means of CRISPR-Cas9 genome editing. Methods: The efficiency of the gene editing machineries were firstly assessed in the adherent human colorectal cancer cell line HCT116 prior to their application on the B-cell lines, which are less amenable to genetic manipulation. TP53 gene removal (15.6 kbp) was performed by transient transfection of a vector encoding Cas9 as well as single guide (sg) RNAs targeting upstream and downstream of the TP53 coding region. For deletion of 17p (20.5 Mbp) sgRNAs targeting exon 2 of GEMIN4 (telomeric) and intron 5 of MAP2K3 (centromeric) were designed. PCR was used to confirm deletions. Results: Isogenic HCT116 cell lines with hemizygous and homozygous TP53 deletion, as well as hemizygous 17p deletion were obtained (Figure 1). HG-3 cells, a CLL cell line, were successfully transduced with inducible-Cas9, and subsequently with the sgRNAs for removal of TP53 and 17p. Keyword: Tumor Biology and Heterogeneity No conflicts of interests pertinent to the abstract.

Insights into the phylogenetic diversity, biological activities, and biosynthetic potential of mangrove rhizosphere Actinobacteria from Hainan Island.

Mangrove rhizosphere soils host diverse Actinobacteria tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of bioactive natural products, including those with potential medicinal applications. In this study, we applied an integrated strategy of combining phylogenetic diversity, biological activities, and biosynthetic gene clusters (BGCs) screening approach to investigate the biotechnological importance of Actinobacteria isolated from mangrove rhizosphere soils from Hainan Island. The actinobacterial isolates were identifified using a combination of colony morphological characteristics and 16S rRNA gene sequence analysis. Based on the results of PCR-detected BGCs screening, type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected. Crude extracts of 87 representative isolates were subjected to antimicrobial evaluation by determining the minimum inhibitory concentration of each strain against six indicator microorganisms, anticancer activities were determined on human cancer cell lines HepG2, HeLa, and HCT-116 using an MTT colorimetric assay, and immunosuppressive activities against the proliferation of Con A-induced T murine splenic lymphocytes in vitro. A total of 287 actinobacterial isolates affiliated to 10 genera in eight families of six orders were isolated from five different mangrove rhizosphere soil samples, specififically, Streptomyces (68.29%) and Micromonospora (16.03%), of which 87 representative strains were selected for phylogenetic analysis. The crude extracts of 39 isolates (44.83%) showed antimicrobial activity against at least one of the six tested indicator pathogens, especially ethyl acetate extracts of A-30 (Streptomyces parvulus), which could inhibit the growth of six microbes with MIC values reaching 7.8 μg/mL against Staphylococcus aureus and its resistant strain, compared to the clinical antibiotic ciproflfloxacin. Furthermore, 79 crude extracts (90.80%) and 48 (55.17%) of the isolates displayed anticancer and immunosuppressive activities, respectively. Besides, four rare strains exhibited potent immunosuppressive activity against the proliferation of Con A-induced T murine splenic lymphocyte in vitro with an inhibition rate over 60% at 10 μg/mL. Type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes were detected in 49.43, 66.67, and 88.51% of the 87 Actinobacteria, respectively. Signifificantly, these strains (26 isolates, 29.89%) harbored PKS I, PKS II, and NRPS genes in their genomes. Nevertheless, their bioactivity is independent of BGCs in this study. Our findings highlighted the antimicrobial, immunosuppressive, and anticancer potential of mangrove rhizosphere Actinobacteria from Hainan Island and the biosynthetic prospects of exploiting the corresponding bioactive natural product.

Design, synthesis of triazole-based scaffolds, N-(substitutedphenyl)-2-(5-(4-methoxyphenyl)-4-phenyl-4H-1,2,4-triazol-3-ylthiol)acetamides: As potential anti-cholinesterase agents for neurodegenerative diseases

Alzheimer's disease (AD) is currently regarded as a global health concern; there are now about 50 million AD patients worldwide, and it is predicted that this number will double every five years and reach 152 million by 2050. Although there are therapies that can help with the symptoms of Alzheimer's disease, there is currently no cure for the condition. This study synthesized a series of novel triazole scaffolds 7a–k, fully characterized, and investigated to unravel their anticholinesterase potential. Density functional theory (DFT) calculations were carried out to investigate the compounds' molecular geometry and electron distribution. The significant enzymatic inhibitory potential was exhibited by compound7c against AChE (IC50 = 9.52 ± 0.25 μM) and 7g against BChE (IC50 = 31.51 ± 0.38 μM), in comparison to the standard drug eserine. Moreover, the compounds were also screened for their anti-proliferative activity against HCT-116 human cancer cell lines, with 7f demonstrating 19.2% cell viability at 25 μM and 28.4% cell viability at 50 μM. The bioactivity results were further validated through computational docking analysis.

Design, synthesis, molecular docking and biological evaluation of novel pyrazole derivatives bearing quinoxalinone moiety as multi-targeted anticancer agents

Based on a multitarget-directed drug design technique, a series of new quinoxalinone-based pyrazole derivatives (4a-h) were designed and synthesized. The potency of newly synthesized molecules to inhibit the antiproliferation of the human cancer cell lines MCF-7 (breast), HCT-116 (colon), and A549 (lung) was examined. The most effective compounds against the examined cancer cell lines were 4e, 4f, 4 g, and 4 h. Among these, compounds 4e and 4 h had a strong anticancer activity that was equivalent to sorafenib. The capacity of the potent compounds (4e, 4f, 4 g, and 4 h) to inhibit the in vitro activity of the thymidylate synthase (TS) enzyme, BRaf, and EGFR kinases was also tested. With IC50 values for the TS enzyme, BRaf kinase, and EGFR kinase ranging from 1.16 to 2.97 μM, 1.28 to 3.69 μM, and 1.93 to 4.28 μM, respectively, all the investigated compounds showed a noticeable inhibitory action. Among the synthesized hybrids, compound 4 h showed IC50 value of 2.04, 2.69 and 1.93 μM against MCF-7, HCT-116, and A549 cell line, respectively, and 1.16, 1.28 and 1.93 nM against TS, BRaf and EGFR kinase enzyme, respectively. All of the synthesized hybrids adhered to Lipinski's guidelines, which suggested that they would have favorable oral drug-like qualities. To determine the probable interaction between the potent compounds and the TS active site, molecular docking study was conducted.

Two new pregnane glycosides from the root of Cynanchum auriculatum

Two new pregnane glycosides (1 and 2), together with four known ones (3– 6), were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae). On the basis of detailed spectroscopic analysis and chemical method, the structures of new compounds were characterized to be metaplexigenin 3-O-β-D-cymaropyranosyl- (1→4)-α-L-diginopyranosyl-(1→4)-β-D-cymaropyranoside (1), metaplexigenin 3-O-α-L-diginopyranosyl-(1→4)-β-D-cymaropyranoside (2). All the isolated compounds (1–6) were tested for their in vitro inhibitory activity against the growth of human colon cancer cell lines HCT-116. Compounds 5 and 6 showed significant cytoxicities with IC50 values of 43.58 µM and 52.21 µM.

Anticancer Activity of Endemic Phlomis Extracts in HCT116 Human Colon Cancer Cells

Aim: Previous studies have reported that Phlomis russeliana shows cytotoxic effects against several cancer cell lines; however, its anti cancer activity on HCT-116 cancer cells has not yet been investigated. Therefore, the present study is designed to explore anti-cancer properties of Phlomis russeliana against HCT-116 human colon cancer cell line and HUVEC normal cell line.
 Material and Methods: HCT-116 cells and HUVECs treated with different concentrations of Phlomis russeliana (2, 4, 6, 8 and 10 mg/ml) and cell viability evaluated by the MTT assay. Anti-migratory and anti-colonigenic effects of Phlomis russeliana were assessed with wound healing and colony formation assays respectively. Quantitative determination of total antioxidant status (TAS), total oxidant status (TOS) and caspase-3 activation were performed with colorimetric Elisa kits.
 Results: Phlomis russeliana significantly decreased cell viability of HCT-116 cells in a concentration dependent and showed weaker toxicity against normal HUVECs. Pholomis russeliana significantly inhibited migration and colony formation potential of HCT-116 cells. A significant increase in caspase-3 activation was observed after treatment with Phlomis russeliana. Phlomis russeliana did not significantly affect the TAS and TOS level in HCT-116 cells.
 Conclusion: These results revealed that Phlomis russeliana showed anti-cancer activity in human colon cancer cells, through the suppression of colony formation, inhibition of migration and induction of caspase-3 activation. Phlomis russeliana, could be a promising source for the development of new anti-cancer agents against cancer.

Isolation of two new trichorzin PA derivatives, trichorzin PA X and XI, from the terrestrial fungus Trichoderma harzianum IFM 66736

Two new octadeca-peptibols, trichorzin PA X and XI (1 and 2), were isolated from the fungus Trichoderma harzianum IFM 66736, which was obtained from the soil collected from the Aobanomori Park in Chiba City, Japan. The structures of the compounds were elucidated using spectral studies, X-ray crystallographic analysis, and MS/MS analysis. Compounds 1 and 2 showed cytotoxicity against human colon cancer cell lines HCT116.