Anti-colon Cancer Research Articles

Optimal β-galactosidases for producing high-titer 3,6-anhydro-L-galactose from red-algal agarobiose.

3,6-Anhydro-L-galactose (L-AHG) is a monomeric sugar in agarose derived from red macroalgae. Owing to its various physiological activities such as anti-inflammation, moisturizing, skin whitening, anti-colon cancer, and anti-cariogenicity, L-AHG is a potential functional ingredient. In our previous study, a simple and efficient two-step L-AHG production process was designed for high-titer L-AHG production, where a single enzyme was used after the liquefaction of agarose by acid prehydrolysis. However, the enzyme used did not completely hydrolyze agarobiose (AB). Therefore, in this study, for the efficient hydrolysis of AB and the high-titer production of L-AHG, various β-galactosidases belonging to glycoside hydrolase families 1, 2, 35, and 42 were compared by testing their substrate specificities and kinetic parameters. Among the five β-galactosidases, Bga42A, originating from Bifidobacterium longum ssp. infantis ATCC 15,697, showed the highest substrate specificity. Consequently, the two-step process utilizing Bga42A as a single enzyme resulted in a high-titer production of L-AHG at 85.9g/L, demonstrating the feasibility of producing L-AHG from agarose. KEY POINTS: • L-AHG derived from red macroalgae has various physiological activities. • Various β-galactosidases were evaluated to efficiently hydrolyze agarobiose. • Bga42A showed the highest substrate specificity against agarobiose. • The highest amount of L-AHG with 85.9g/L was simply produced.

A network pharmacology approach and experimental validation to investigate the anticancer mechanism and potential active targets of ethanol extract of Wei-Tong-Xin against colorectal cancer through induction of apoptosis via PI3K/AKT signaling pathway

Ethnopharmacological relevanceWei-Tong-Xin (WTX), derives from the Chinese herbal decoction (CHD) of Wan-Ying-Yuan in ancient China, has been shown to be effective therapeutic herbal decoction for treating gastrointestinal diseases. Present studies have demonstrated that WTX had potential to alleviate the symptoms of gastrointestinal inflammation, gastric ulcer and improve gastric motility. Aim of the studyThe study primarily focused on exploring the therapeutic effect and possible pharmacological mechanism of WTX on colorectal cancer (CRC) based on network pharmacology, in vitro and in vivo experiments. Materials and methodsFirstly, colorectal cancer and WTX associated with targets were searched from GeneCards database and TCM Systems Pharmacology Database and Analysis Platform (TCMSP) respectively. The protein–protein interaction (PPI) network also was constructed to screening key targets. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to predict the underlying biological function and mechanism involving in the anti-colorectal cancer effect of WTX. Next, CCK-8, colony formation and transwell assays were performed to verify the influence of proliferation and metastasizing ability of HCT116 cells after treated with WTX. Cell cycle, apoptosis and reactive oxygen species (ROS) were analysis by flow cytometry. Hoechst 33258 staining was conducted to observe nuclear morphology changes. Protein expression of apoptosis and PI3K/AKT signaling as well as mRNA expression of ferroptosis and apoptosis were determined by Western Blotting and RT-qPCR. The effects of WTX and LY294002 combination on the PI3K/Akt/mTOR signaling pathway were measured by Western Blotting. Finally, the xenograft tumor mouse model was established by subcutaneous injection of CT26 cells to measure tumors volume and weight. Hematoxylin and eosin (HE) staining and immunohistochemical analysis were used to observe the pathological changes and the protein expression in tumor tissues. ResultsThere were 286 potential treatment targets from 130 bioactive compounds in WTX, 1349 CRC-related targets were identified. Eleven core targets (TP53, AKT1, STAT3, JUN, TNF, HSP90AA1, IL-6, MAPK3, CASP3, EGFR, MYC) were found by PPI network analysis constructed of 142 common targets. The results of KEGG enrichment displayed PI3K/AKT signaling pathway as core pathway. After the treatment of WTX, the inhibitory of viability, metastases and cell cycle arrest at G2/M phase were observed in HCT116 cells. Moreover, WTX induced an increase in the expression of apoptosis proteins (Bak, cytochrome c, cleaved caspase-9/caspase-9 and cleaved caspase-3/caspase-3) and the levels of ROS and MDA, a decrease in the expression of PI3K/AKT signaling related proteins (PI3K, p-PI3K, p-AKT/AKT and p-mTOR/mTOR) and the level of SOD. WTX treatment significantly reduced the tumor weight, increased cleaved caspase-3 positive area and decreased that of ki67 in xenograft mouse model. ConclusionThrough a network pharmacology approach and in vitro experiments, we predicted and verified the effect of WTX on colorectal cancer cells mainly depended on the regulation of intrinsic apoptosis via PI3K/AKT signaling pathway, and further animal experiments proved that WTX has a good anti-colon cancer effect in vivo.

Apoptosis Potency Prediction of Steroid Saponin from Gembili (Dioscorea esculenta) as Bcl-2 and Bcl-xL Inhibitors in Colon Cancer

Steroid saponins from gembili tuber (Dioscorea esculenta) are natural compounds that are known to have anticancer activity by inducing apoptosis through inhibition of Bcl-2 dan Bcl-xL. This study was determine the potency, mechanism and binding affinity of steroid saponin compounds as Bcl-2 and Bcl-xL inhibitor of colon cancer in silico using molecular docking. In silico assay was carried out using VEGAZZ (use for Bcl-2 protein preparation), Open Babel (use for minimizing the 3D structure of steroid saponin compounds), Autodock Vina in the PyRx 0.8 program (use for molecular docking), and PyMOL, Discovery Studio Visualizer (use for 2D and 3D visualization). The result of molecular docking was a binding affinity value based on the formation of hydrogen and hydrophobic interactions between ligand and receptor, more smaller binding affinity value, more stronger the bond. Data were compared with navitoclax, ABT-737 and obatoclax. The binding affinity between Bcl-2 and navitoclax, ABT-737, obatoclax, prosapogenin A, dioscin, gracillin, diosgenin, protogracillin, dichotomin and protodioscin were –9,8; –8,9; –7,2; –9,0; –8,8; –8,0; –7,9; –8,4; –8,2 and –7,7 kcal/mol. Then the binding affinity between Bcl-xL and navitoclax, ABT-737, obatoclax, prosapogenin A, dioscin, gracillin, diosgenin, protogracillin, dichotomin, and protodioscin were –10,6; –9,3; –8,3; –9,7; –9,4; –8,9; –9,7; –9,1; –9,9 and –8,8 kcal/mol. Based on the results obtained, the steroid saponin compounds of gembili tuber are possible have potential as anti-colon cancer through inhibition of Bcl-2 and Bcl-xL protein in order to increase the regulation of apoptosis. HIGHLIGHTS The main process of apoptosis in the intrinsic pathway is regulated by the Bcl-2 protein family Saponin steroids are triterpenoid modifications commonly found in Dioscoreacease plants including Dioscorea esculenta Steroid saponins compounds of gembili tuber include prosapogenin A, dioscin, gracillin, diosgenin, protogracillin, dichotomin and protodioscin has potential as an anti-colon cancer through inhibition of anti-apoptotic proteins Bcl-2 and Bcl-xL in silico using molecular docking GRAPHICAL ABSTRACT

Ultrasound changes of the gallbladder and pancreas in the children with cystic fibrosis

This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action.Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM).Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53+/+ colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells.The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity.

White tea extract modified green synthesis of magnetite supported Ag nanoparticles: Evaluation of its catalytic activity, antioxidant and anti-colon cancer effects

In this study, an eco-friendly and low-cost procedure for the synthesis of White tea plant extract modified magnetic nanocomposite (Fe 3 O 4 @ W.tea ) has been demonstrated. Ag nanoparticles (Ag NPs) were further decorated in situ over the designed Fe 3 O 4 @ W.tea nanocomposite exploiting the plant derived phytochemicals as bio-reductant and stabilizer. The resulting Fe 3 O 4 @ W.tea /Ag nanocomposite was characterized by various analytical methods like Fourier Transformed Infra Red (FT-IR) spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), energy dispersive X-ray analysis (EDX) elemental mapping, transmission electron microscopy (TEM), vibrating-sample magnetometer (VSM), X-ray diffraction analysis (XRD), and inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. The as-synthesized bio-nanomaterial was used as an excellent heterogeneous and magnetically retrievable catalyst in the three-component condensation of 4-hydroxycoumarin, malononitrile and various aldehydes in refluxing aqueous media. A broad range of aromatic aldehydes underwent the reaction to produce diverse pyrano[3,2- c ]chromene derivatives in very good yields irrespective of the nature of bearing functional groups or their respective geometrical positions. Due to superparamagnetic character, the material was easily magnetically decanted out and recycled for 8 successive times with preservation of its catalytic activity. After the chemical applications we also explored the material biologically in the resistance of human colon cancer and thereby studied the cytotoxicity over two standard cell lines, HT-29 and Caco-2. The conventional MTT assay was carried out over them which revealed an increase in % cell viability dose dependently. The IC 50 values observed in the two cell lines were 384.2 μg/ml and 254.6 μg/ml respectively. In addition, DPPH radical scavenging test was performed for studying anti-oxidant activity. The results validate the administration of Fe 3 O 4 @ W.tea /Agnanocomposite as a competent colon protective drug in the clinical trial studies over human.

Kaempferol suppression of acute colitis is regulated by the efflux transporters BCRP and MRP2

The bioavailability of most flavonoids is low but effective in vivo; however, the mechanism of the efficacy of flavonoids has not been elucidated. Kaempferol is typical flavonoids., preliminary research indicates that kaempferol has a significant anti-colon cancer and anti-inflammatory effect. We reported previously that the triple recycling pathways significantly increase the local bioavailability of flavonoids and prolong the residence time of flavonoids in the liver and intestines, which is likely the mode by which flavonoids exert local efficacy. Notably, Efflux transporters (ETs), such as Breast cancer resistance protein (BCRP) and Multi drug resistance-associated protein 2 (MRP2), are the main regulatory molecules of the enterohepatic triple recycling pathways. Thus, our current study explored the regulation of kaempferol by BCRP and MRP2 and the role of BCRP and MRP2 in the suppression of Dextran sulfate sodium (DSS)-induced colitis by kaempferol. Herein, four mouse model was constructed, and the Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was established to simultaneously quantify kaempferol and its 3 metabolites and investigate the oral pharmacokinetic characteristics and tissue distribution of these compounds. In Bcrp−/−-Mrp2−/− mice, the movement of kaempferol via the enterohepatic triple recycling was blocked, and the preventative and therapeutic effects of this compound on acute colitis were inhibited. BCRP and MRP2 defects hindered the efflux of kaempferol and its phase II metabolites and increased the plasma levels. Our study revealed that the disposal of kaempferol was regulated by the ETs BCRP and MRP2, and most importantly, the results will help elucidate the mechanism by which kaempferol suppresses the transformation of colitis into colon cancer.

Integrated network pharmacology and serum metabolomics approach deciphers the anti-colon cancer mechanisms of Huangqi Guizhi Wuwu Decoction.

Huangqi Guizhi Wuwu Decoction (HGWD), as a classic Chinese herbal decoction, has been widely used in treating various diseases for hundreds of years. However, systematically elucidating its mechanisms of action remains a great challenge to the field. In this study, taking advantage of the network pharmacology approach, we discovered a potential new use of HGWD for patients with colon cancer (CC). Our in vivo result showed that orally administered HGWD markedly inhibited the growth of CC xenografts in mice. The subsequent enrichment analyses for the core therapeutic targets revealed that HGWD could affect multiple biological processes involving CC growth, such as metabolic reprogramming, apoptosis and immune regulation, through inhibiting multiple cell survival-related signalings, including MAPK and PI3K-AKT pathways. Notably, these in silico analysis results were most experimentally verified by a series of in vitro assays. Furthermore, our results based on serum metabolomics showed that the lipid metabolic pathways, including fatty acid biosynthesis and cholesterol metabolism, play key roles in delivery of the anti-CC effect of HGWD on tumor-bearing mice, and that cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a potential therapeutic target. Together, our integrated approach reveals a therapeutic effect of HGWD on CC, providing a valuable insight into developing strategies to predict and interpret the mechanisms of action for Chinese herbal decoctions.

Probiotics as multifaceted oral vaccines against colon cancer: A review.

Probiotics are known as the live microorganisms that, upon adequate administration, elicit a health beneficial response inside the host. The probiotics are known as immunomodulators and exhibit anti-tumor properties. Advanced research has explored the potential use of probiotics as the oral vaccines without the latent risks of pathogenicity. Probiotic-based oral vaccines are known to induce mucosal immunity that prevents the host from several enteric infections. Probiotic bacteria have the ability to produce metabolites in the form of anti-inflammatory cytokines, which play an important role in the prevention of carcinogenesis and in the activation of the phagocytes that eliminate the preliminary stage cancer cells. This review discusses the advantages and disadvantages of using the oral probiotic vaccines as well as the mechanism of action of probiotics in colon cancer therapy. This review also employs the use of “PROBIO” database for selecting certain probiotics with immunomodulatory properties. Furthermore, the use of several probiotic bacteria as anti-colon cancer adjuvants has also been discussed in detail. Because the current studies and trials are more focused on using the attenuated pathogens instead of using the probiotic-based vaccines, future studies must involve the advanced research in exploiting the potential of several probiotic strains as adjuvants in cancer therapies.

Green synthesis of Cu/Fe3O4 nanoparticles using green tea extract: Evaluation of its catalytic activity, antioxidant and anti-colon cancer effects

• Green synthesis of Cu/Fe 3 O 4 nanoparticles using green tea extract. • Green tea extract was used as a green reducing agent and an excellent stabilizer. • Fe 3 O 4 @ G.tea /Cu nanocomposite have a suitable anticancer activity against colon cell lines. • Fe 3 O 4 @ G.tea /Cu nanocomposite have good antioxidant activity. A sustainable biogenic synthesis for the preparation of green tea plant extract engineered novel magnetic nanocomposite (Fe 3 O 4 @ G.tea ) has been represented in this research. The biocompatible composite was then fabricated with in situ prepared Cu NPs using the green tea derived biomolecules avoiding any harsh chemicals, thus making the procedure absolutely green. The electron rich phytochemicals were additionally used to stabilize the adorned NPs from aggregation or aerial oxidation. Physicochemical features of the ensuing Fe 3 O 4 @ G.tea /Cu nanomaterial was ascertained over a range of instrumental methods, viz., FT-IR, SEM, EDX, elemental mapping, TEM, VSM, XRD, and ICP-AES analysis. Catalytic properties of the bio-nanomaterial were assessed by the synthesis of diverse pyrano[3,2- c ]chromene moieties following a multicomponent reaction (MCR) under eco-friendly conditions. Diverse aromatic and heteroaromatic aldehydes were used in the reaction to afford the products in excellent yields. Reusability of the nanocatalyst was demonstrated by easy magnetic decantation from the reaction medium and subsequent recycling for 8 consecutive runs without considerable loss in its activity. Furthermore, the Fe 3 O 4 @ G.tea /Cu bio-nanomaterial was employed in the biological evaluation against reducing the proliferation of human colorectal cancer and investigating the cytotoxicity against two colorectal cell lines, HT-29 and Caco-2 respectively following MTT assay. The studies documented an increase in % cell viability with increase in material concentration and the corresponding IC 50 values obtained as 384.2 μg/ml and 254.6 μg/ml respectively. Again, anti-oxidant activity of the material was determined by DPPH radical scavenging analysis.

Anti-Colon Cancer Activity of Patrinia villosa Extract and Analysis of its Components based on UPLC-QTOF-MS/MS

Anti-Colon Cancer Activity of Patrinia villosa Extract and Analysis of its Components based on UPLC-QTOF-MS/MS

Natural Small Molecules in Gastrointestinal Tract and Associated Cancers: Molecular Insights and Targeted Therapies.

Gastric cancer is one of the most common cancers of the gastrointestinal tract. Although surgery is the primary treatment, serious maladies that dissipate to other parts of the body may require chemotherapy. As there is no effective procedure to treat stomach cancer, natural small molecules are a current focus of research interest for the development of better therapeutics. Chemotherapy is usually used as a last resort for people with advanced stomach cancer. Anti-colon cancer chemotherapy has become increasingly effective due to drug resistance and sensitivity across a wide spectrum of drugs. Naturally-occurring substances have been widely acknowledged as an important project for discovering innovative medications, and many therapeutic pharmaceuticals are made from natural small molecules. Although the beneficial effects of natural products are as yet unknown, emerging data suggest that several natural small molecules could suppress the progression of stomach cancer. Therefore, the underlying mechanism of natural small molecules for pathways that are directly involved in the pathogenesis of cancerous diseases is reviewed in this article. Chemotherapy and molecularly-targeted drugs can provide hope to colon cancer patients. New discoveries could help in the fight against cancer, and future stomach cancer therapies will probably include molecularly formulated drugs.

Anticolon Cancer Effect of Korean Red Ginseng via Autophagy- and Apoptosis-Mediated Cell Death.

Ginseng (Panax ginseng Meyer) has been used in East Asian traditional medicine for a long time. Korean red ginseng (KRG) is effective against several disorders, including cancer. The cytotoxic effects of KRG extract in terms of autophagy- and apoptosis-mediated cell death and its mechanisms were investigated using human colorectal cancer lines. KRG induced autophagy-mediated cell death with enhanced expression of Atg5, Beclin-1, and LC3, and formed characteristic vacuoles in HCT-116 and SNU-1033 cells. An autophagy inhibitor prevented cell death induced by KRG. KRG generated mitochondrial reactive oxygen species (ROS); antioxidant countered this effect and decreased autophagy. KRG caused apoptotic cell death by increasing apoptotic cells and sub-G1 cells, and by activating caspases. A caspase inhibitor suppressed cell death induced by KRG. KRG increased phospho-Bcl-2 expression, but decreased Bcl-2 expression. Moreover, interaction of Bcl-2 with Beclin-1 was attenuated by KRG. Ginsenoside Rg2 was the most effective ginsenoside responsible for KRG-induced autophagy- and apoptosis-mediated cell death. KRG induced autophagy- and apoptosis-mediated cell death via mitochondrial ROS generation, and thus its administration may inhibit colon carcinogenesis.

A novel approach of encapsulating curcumin and succinylated derivative in mannosylated-chitosan nanoparticles

Curcumin (CUR) manifests anti-colon cancer activity but suffers from low solubility, bioavailability, and instability, rendering it not as effective as its chemotherapeutic cousins. Here, we conjugate CUR to succinic anhydride (SA), (CUR.SA conjugate), subsequently formulated in mannose-conjugated chitosan nanoparticles (CUR-NPs and CUR.SA-NPs). Instrumental analyses confirmed formation of CUR.SA and mannosylated chitosan (CM) conjugates, with CUR.SA being less crystalline thus, more soluble. Average particle size of CUR-NPs and CUR.SA-NPs were 268 ± 6 nm and 342 ± 4.6 nm, with drug entrapment of 93.34 ± 0.40 % and 98.46 ± 0.06 % respectively. In vitro releases of CUR and CUR.SA from nanoparticles in pH 1.2 and 6.8 media were slow and sustained over 2 h and 72 h, respectively. The physical characteristics of the nanoparticles were unchanged over 3 weeks of storage. Thus, a successful CUR.SA conjugate has been developed, couriered in CM nanoparticles, with favorable attributes that warrant further anti-colon cancer studies, which is ongoing.

Lentinan-functionalized selenium nanoparticles induce apoptosis and cell cycle arrest in human colon carcinoma HCT-116 cells.

Selenium nanoparticles (SeNPs) have gained extensive attention for their excellent biological activity and low toxicity. However, SeNPs are extremely liable to aggregate into non-bioactive or gray elemental selenium, which limits their application in the biomedicine field. This study aimed to prepare stable SeNPs by using lentinan (LNT) as a template and evaluate its anti-colon cancer activity. The average particle diameter of obtained lentinan-selenium nanoparticles (LNT-SeNPs) was approximately 59 nm and presented zero-valent, amorphous, and spherical structures. The monodisperse SeNPs were stabilized by LNT through hydrogen bonding interactions. LNT-SeNPs solution remained highly stable at 4°C for at least 8 weeks. The stability of LNT-SeNPs solution sharply decreased under high temperature and strong acidic conditions. LNT-SeNPs showed no obvious cytotoxic effect on normal cells (IEC-6) but significantly inhibited the proliferation of five colon cancer cells (HCT-116, HT-29, Caco-2, SW620, and CT26). Among them, LNT-SeNPs exhibited the highest sensitivity toward HCT-116 cells with an IC50 value of 7.65 μM. Also, LNT-SeNPs displayed better cancer cell selectivity than sodium selenite and selenomethionine. Moreover, LNT-SeNPs promoted apoptosis of HCT-116 cells through activating mitochondria-mediated apoptotic pathway. Meanwhile, LNT-SeNPs induced cell cycle arrest at G0/G1 phase in HCT-116 cells via modulation of cell cycle regulatory proteins. The results of this study indicated that LNT-SeNPs possessed strong potential application in the treatment of colorectal cancer (CRC).

Biocompatibility and colorectal anti-cancer activity study of nanosized BaTiO3 coated spinel ferrites

In the present work, different nanoparticles spinel ferrite series (MFe2O4, Co0.5M0.5Fe2O4; M = Co, Mn, Ni, Mg, Cu, or Zn) have been obtained via sonochemical approach. Then, sol–gel method was employed to design core–shell magnetoelectric nanocomposites by coating these nanoparticles with BaTiO3 (BTO). The structure and morphology of the prepared samples were examined by X-ray powder diffraction (XRD), scanning electron microscope (SEM) coupled with energy dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscope (HR-TEM), and zeta potential. XRD analysis showed the presence of spinel ferrite and BTO phases without any trace of a secondary phase. Both phases crystallized in the cubic structure. SEM micrographs illustrated an agglomeration of spherical grains with nonuniformly diphase orientation and different degrees of agglomeration. Moreover, HR-TEM revealed interplanar d-spacing planes that are in good agreement with those of the spinel ferrite phase and BTO phase. These techniques along with EDX analyses confirmed the successful formation of the desired nanocomposites. Zeta potential was also investigated. The biological influence of (MFe2O4, CoMFe) MNPs and core–shell (MFe2O4@BTO, CoMFe@BTO) magnetoelectric nanocomposites were examined by MTT and DAPI assays. Post 48 h of treatments, the anticancer activity of MNPs and MENCs was investigated on human colorectal carcinoma cells (HCT-116) against the cytocompatibility of normal non-cancerous cells (HEK-293). It was established that MNPs possess anti-colon cancer capability while MENCs exhibited a recovery effect due to the presence of a protective biocompatible BTO layer. RBCs hemolytic effect of NPs has ranged from non- to low-hemolytic effect. This effect that could be attributed to the surface charge from zeta potential, also the CoMnFe possesses the stable and lowest zeta potential in comparison with CoFe2O4 and MnFe2O4 also to the protective effect of shell. These findings open up wide prospects for biomedical applications of MNPs as anticancer and MENCs as promising drug nanocarriers.

Bioactivity of hamamelitannin, flavokawain A, and triacetyl resveratrol as natural compounds: Molecular docking study, anticolon cancer, and anti-Alzheimer potentials.

In this study, we worked on anticolon cancer effects and anti-Alzheimer's disease with molecular docking studies. Hamamelitannin, flavokawain A, and triacetyl resveratrol compounds showed good inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. The inhibition effects of flavokawain A, hamamelitannin, and triacetyl resveratrol on AChE and BuChE enzymes were determined spectrophotometrically conforming to Ellman. IC50 values of these enzymes were ranging between 0.95±0.12 and 93.27±8.14nM for AChE and 5.71±0.77 and 52.10±8.41nM for BuChE. The inhibitory activities of some chemical compounds such as flavokawain A, hamamelitannin, and triacetyl resveratrol were assessed by performing the molecular docking study in the presence of AChE and BuChE. Also, the features of the ligand-enzyme complex had value of -7.722kcal/mol for flavokawain A against AChE and -5.530kcal/mol against BuChE. The molecular docking calculations indicated the probable interactions and their characteristics at an atomic level. Due to the outcomes gained from docking, the affinity of the chemical compounds to the enzymes was considerable. In vitro cell viabilities of flavokawain A, hamamelitannin, and triacetyl resveratrol with various concentrations on SW620, DLD-1, HT29, HCT8, and HCT116 were investigated by MTT assay with Doxorubicin as the control compound.

Anti-Inflammatory and Anti-Colon Cancer Activities of Mung Bean Grown in Burkina Faso.

Widely used in traditional medicine in Asia and recently introduced in Burkina Faso under the name Beng-tigré, mung bean is a legume consumed throughout the world and more so in India. The objective of this study was to evaluate the cytotoxicity of the mung bean grown and consumed in Burkina Faso and to study its biological properties such as anti-inflammatory and anticancer activity of the natural and sprouted seeds. The cytotoxicity of the extracts was tested on Artemia salina larvae, and the anti-inflammatory activity was evaluated in vitro by albumin denaturation method using diclofenac as reference molecule. The anticancer activity of hydro-ethanol extracts was evaluated on rats made cancerous with 1,2-dimethylhydrazine (DMH) using 5-fluorouracil as reference molecule. The results showed that the highest yield of the plant extraction was observed with the hydro-ethanol solvent, both for the natural form of mung bean (MBN) and for its sprouted form (MBG). The cytotoxicity test showed no toxicity of the extracts toward shrimp larvae. The ethanolic extract of germinated mung bean seeds gave the highest anti-inflammatory activity at 95.13 ± 0.22% inhibition with significant difference (p < 0.05) between the extracts. Cancer induction with DMH was inhibited by both MBN and MBG extracts. The test of preventive effects of the extracts showed the best activity with significant difference in biochemical results. These results confirm that the mung bean grown in Burkina Faso, as a nontoxic legume, is a functional food that can be integrated into the population's dietary habits for a double interest. Moreover, they open perspectives for the research of active principles of plant origin with anti-inflammatory and anticancer properties.

Network pharmacology and molecular docking to elucidate the mechanism of pulsatilla decoction in the treatment of colon cancer.

Objective: Colon cancer is a malignant neoplastic disease that seriously endangers the health of patients. Pulsatilla decoction (PD) has some therapeutic effects on colon cancer. This study is based on the analytical methods of network pharmacology and molecular docking to study the mechanism of PD in the treatment of colon cancer. Methods: Based on the Traditional Chinese Medicine Systems Pharmacology Database, the main targets and active ingredients in PD were filtered, and then, the colon cancer-related targets were screened using Genecards, OMIM, PharmGKB, and Drugbank databases. Then, the screened drug and disease targets were Venn analyzed to obtain the intersection targets. Cytoscape software was used to construct the “Components–Targets–Pathway” map, and the String database was used to analyze the protein interaction network of the intersecting targets and screen the core targets, and then, the core targets were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was implemented using AutoDockTools to predict the binding capacity for the core targets and the active components in PD. Results: Sixty-five ingredients containing 188 nonrepetitive targets were screened and 180 potential targets of PD anticolon cancer were identified, including 10 core targets, namely, MAPK1, JUN, AKT1, TP53, TNF, RELA, MAPK14, CXCL8, ESR1, and FOS. The results of GO analysis showed that PD anticolon cancer may be related to cell proliferation, apoptosis, energy metabolism, immune regulation, signal transduction, and other biological processes. The results of KEGG analysis indicated that the PI3K-Akt signaling pathway, MAPK signaling pathway, proteoglycans in cancer, IL-17 signaling pathway, cellular senescence, and TNF signaling pathway were mainly involved in the regulation of tumor cells. We further selected core targets with high degree values as receptor proteins for molecular docking with the main active ingredients of the drug, including MAPK1, JUN, and AKT1. The docking results showed good affinity, especially quercetin. Conclusion: This study preliminarily verified that PD may exert its effect on the treatment of colon cancer through multi-ingredients, multitargets, and multipathways. This will deepen our understanding of the potential mechanisms of PD anticolon cancer and establish a foundation for further basic experimental research.

A natural halogenated fluoride adenosine analog 5'-fluorodeoxy adenosine induced anticolon cancer activity in vivo and in vitro.

Adenosine (ADO) and its analogs have been introduced into the anticancer clinical trials, especial for the ADO derivatives with fluoride. The biosynthesis of fluorinase produces a fluorine-containing ADO analog 5'-fluorodeoxy adenosine (5'-FDA). The toxicity and application of 5'-FDA has not been evaluated, which limits the application of ADO analogs. In order to study its potential mechanism, we carried out the following experiments. In our research, 5'-FDA displayed good antitumor activity in colon cancer cells and two colon cancer models. As a result, 5'-FDA concentration-dependently inhibited the proliferation, migration, and invasion in colon cancer cells through its proapoptosis and cell cycle arrest pathway. Furthermore, 5'-FDA inhibited the growth of colon cancer and its pulmonary metastasis in CT26 inbred mice without affecting their body weight. It was found that 5'-FDA remarkably increased the protein levels of Caspase 3 and cleaved-Caspase 9 and decreased Cyclin A2 and CDK2 via the regulation of p53 signaling pathway, and increased the protein levels of Caspase 8 and cleaved-Caspase 8 which participated in apoptosis pathway. All in all, 5'-FDA displayed excellent therapeutic effects on colon cancer and its pulmonary metastasis. We believed that our study provided a theoretical basis for further preclinical research of 5'-FDA in the treatment of cancer.

Thymidine Kinase 1 Mediates the Synergistic Antitumor Activity of Ubenimex and Celecoxib via Regulation of Cell Cycle in Colorectal Cancer.

Colorectal cancer (CRC) is a common clinical malignant tumor of the digestive system that seriously affects the health and life of patients. Because it is difficult to cure CRC, the strategy of drug combination is often used in clinical therapy. This study mainly revealed that ubenimex and/or celecoxib exerted anti-colon cancer effects in vitro and in vivo, and the efficacy was significantly enhanced when the two drugs were combined. The combination of the two drugs induced significantly stronger cell-cycle arrest than did the single drug, and also enhanced the antitumor efficacy of 5-fluorouracil and its derivatives. At the same time, the expression of thymidine kinase 1 (TK1) protein was decreased through regulating the level of TK1 mRNA treated with celecoxib and/or ubenimex, but the combination drugs exhibited much more reduction of TK1 mRNA and protein as compared with the single agent alone. TK1 may be the molecular target of the combination of two drugs to exert the anti-colorectal cancer effect. In summary, this research demonstrates that celecoxib combined with ubenimex inhibits the development of colorectal cancer in vitro and in vivo, making them a viable combination regimen. SIGNIFICANCE STATEMENT: In this study, our data reveal the great potential of celecoxib combined with ubenimex in the treatment of colorectal cancer, providing new ideas for clinical antitumor drug regimens and theoretical reference for drug development.