Potato protease inhibitors,a functional food material with antioxidant and anticancer potential

Potato protease inhibitors(PPIs),as the main component of potato protein isolate,have good safety,nutrition and great market potential.The antioxidant and anticancer properties of PPIs were evaluated with cellbased biological assays.The results showed that when the concentration of PPIs was 5 mg/mL,the peroxyl radical scavenging value was(2119±204)mg VCE/100 g,and the cellular antioxidant activity values were(45.83±3.5)(no PBS wash)and(33.25±4.4)μmol QE/100 g(PBS wash).Cells pretreated with PPIs could significantly prevent the oxidative damage induced by H_(2)O_(2),inhibit the morphological changes of cells and maintain the integrity.Furthermore,PPIs had selective anti-proliferative effects on GIST882 cells(IC50=(10.53±3.87)mg/mL)and demonstrated potent inhibition of the growth,migration and invasion of cancer cells.These findings provide a scientific basis for PPIs as promising candidates for functional foods to aid in the prevention of oxidative damage and cancer.

Thymoquinone enhances the antioxidant and anticancer activity of Lebanese propolis

BACKGROUND Reactive oxygen species(ROS)are produced by multiple cellular processes and are maintained at optimal levels in normal cells by endogenous antioxidants.In recent years,the search for potential exogenous antioxidants from dietary sources has gained considerable attention to eliminate excess ROS that is associated with oxidative stress related diseases including cancer.Propolis,a resinous honeybee product,has been shown to have protective effects against oxidative stress and anticancer effects against several types of neoplasms.AIM To investigate the antioxidant and anticancer potential of Lebanese propolis when applied alone or in combination with the promising anticancer compound Thymoquinone(TQ)the main constituent of Nigella sativa essential oil.METHODS Crude extracts of Lebanese propolis collected from two locations,Rashaya and Akkar-Danniyeh,were prepared in methanol and the total phenolic content was determined by Folin–Ciocalteu method.The antioxidant activity was assessed by the ability to scavenge 2,2-diphenyl-1-picrylhydrazyl(DPPH)free radical and to inhibit H2O2-induced oxidative hemolysis of human erythrocytes.The anticancer activity was evaluated by[3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide]MTT assay against HCT-116 human colorectal cancer cells and MDAMB-231 human breast cancer cells.RESULTS The total phenolic content of propolis extract from Rashaya and Akkar-Danniyeh were 56.81μg and 83.503μg of gallic acid equivalent/mg of propolis,respectively.Both natural agents exhibited strong antioxidant activities as evidenced by their ability to scavenge DPPH free radical and to protect erythrocytes against H2O2-induced hemolysis.They also dose-dependently decreased the viability of both cancer cell lines.The IC50 value of each of propolis extract from Rashaya and Akkar-Danniyeh or TQ was 22.3,61.7,40.44μg/mL for breast cancer cells at 72 h and 33.3,50.9,33.5μg/mL for colorectal cancer cells at the same time point,respectively.Importantly,the inhibitory effects of propolis on DPPH radicals and cancer cell viability were achieved at half its concentration when combined with TQ.CONCLUSION Our results indicate that Lebanese propolis extract has antioxidant and anticancer potential and its combination with TQ could possibly prevent ROS-mediated diseases.

Anticancer Activities of Substituted Cinnamic Acid Phenethyl Esters on Human Cancer Cell Lines

Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10 μmol·L -1 the lead compound CAPE possessed anticancer activities against human HL 60, Bel 7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel 7402 and Hela cell lines.

Purification and Characterization of Cytotoxins from Agkistrodon acutus Venom and Their Anticancer Activity

Aim To investigate the anticancer activity of two new cytotoxins from thevenom of Agkistrodon acutus. Methods The venom was isolated by FPLC column chromatography consistingof DEAE Sepharose FF and Source 30S. The cytotoxic activity on tumor cells was detected by MITmethod. Purity and molecular weight were determined by SDS-PAGE (silver staining). Their stabilitiesto temperature and pH were also detected. Results Two pure cytotoxins named ACTX-6 and ACTX-8 wereobtained. Their molecular weights are 98 kDa and 27 kDa, respectively. ACTX-6 consists of twosubunits bonded together by disulfide bonds. Conclusion ACTX-6 and ATCX-8 have highest inhibitoryactivity on lung cancer cell A549. ACTX-6 is stable to heat while ACTX-8 not. ACTX-6 is stablebetween pH 7-9 and ACTX-8 between pH 6 - 9.

Cantharidin and Its Analogues:Anticancer and Ser/Thr Protein Phosphatase Inhibitory Activities

This paper mainly describes the anticancer activities and Ser/Thr protein phosphatase inhibitory activities of cantharidin and its analogues.

Synthesis and Anticancer Effect of gem-Difluoromethylenated Chrysin Derivatives

Ten gem-difluoromethylenated chrysin derivatives were prepared and their anticancer activities in vitro were evaluated by the standard MTT method. The results of biological test showed that some of gem-difluoromethylenated chrysin derivatives had higher anticancer activity than chrysin.

Synthesis and anticancer activities of porphyrin induced anticancer drugs

In view of the property of porphyrin＇s accumulation selectively in tumor, the ftorafur was modified by binding a porphyrin block to improve its tumor targeting and reduce its side effects. These novel porphyrin derivatives and metal compounds were synthesized under mild conditions with satisfactory yield, and the constructions of all these new compounds were characterized by UV, IR, MS, ^1H NMR spectra and elementary analysis. Their anticancer activities were evaluated by MTT assay; the results indicated that the anticancer activities of compounds 4a-e were twice as high as that of ftorafur.

Total synthesis and anticancer activity studies of the stereoisomers of asperphenamate and patriscabratine

All stereoisomers of asperphenamate 1a and patriscabratine 2a were achieved with a high yield,and total synthesis of 2a is firstly described here.The absolute configuration of patriscabratine was determined as(S,S).The compounds 1a-d and 2a-d have been tested by MTT assay in T47D,MDA-MB231,HL60,Hela and SGC-7901 cell lines in vitro.Among them,the(R,S) stereoisomer shows the strongest anticancer effects,while the(S,R) shows the weakest one.

The Anticancer Activities Phenolic Amides from the Stem of Lycium barbarum

Four new phenolic amides,4-O-methylgrossamide(1),(E)-2-(4,5-dihydroxy-2-{3-[(4-hydrox-yphenethyl)amino]-3-oxopropyl}-phenyl)-3-(4-hydroxy-3-methoxyphenyl)-N-(4-hydroxyphenethyl)acryl-amide(2),(Z)-lyciumamide C(3),(Z)-thoreliamide B(4),together with thirteen known phenolic amides were identified from the stem of Lycium barbarum.The structures of the new compounds were determined by spectroscopic methods.All compounds were evaluated for their anti-cancer activities against human glioma stem cell lines.

Sulforaphene in Raphanus sativus L. var. caudatus Alef increased in late-bolting stage as well as anticancer activity

Objectives: To evaluate the concentration differences of sulforaphene and sulforaphane at various ages and in different parts of Raphanus sativus L. var. caudatus with respect to their potential cancer preventive effect on HCT116 colon cancer cells.Methods: FTIR–ATR and GC–MS were used to characterize the isothiocyanates in the plant extracts followed by HPLC for quantification. Antiproliferation and apoptosis induction were determined by using MTT assay and flow cytometry, respectively.Results: The respective rank of anticancer activity of Raphanus sativus were as follows:vegetative(3 week) < older rosette(4 week) < early-bolting(5 week) < senescence(7 week) < late-bolting(6 week). The low to high concentration of sulforaphene and sulforaphane occurred in the same stage order.Conclusions: The reproductive parts(flower, pod, and dry seed) of Raphanus sativus have the greatest isothiocyanate concentration, evidenced by a sulforaphene concentration higher than the sulforaphane. This result should inform the selection of the most appropriate harvesting stage and plant part for use as a potential chemopreventive agent.

Novel therapeutic diiminoquinone exhibits anticancer effects on human colorectal cancer cells in two-dimensional and threedimensional in vitro models

BACKGROUND Colorectal cancer(CRC) is the second leading cause of cancer-related mortality.Cancer stem cells(CSCs) in CRC, which are spared by many chemotherapeutics,have tumorigenic capacity and are believed to be the reason behind cancer relapse. So far, there have been no effective drugs to target colon CSCs. Diiminoquinone(DIQ) has shown promising effects on targeting colon cancer.However, there is limited research on the effects of DIQ on eradicating CSCs in CRC.AIM To investigate the anticancer potential of DIQ on colon CSCs in two-dimensional(2D) and three-dimensional(3D) models using colonospheres and patient-derived organoids.METHODS Various 2D methods have been used to assess the effect and the mechanism of DIQ on HCT116and HT29 cell lines including cell proliferation and viability assays, migration and invasion assays,immunofluorescence staining, and flow cytometry. The potency of DIQ was also assessed in 3D culture using the sphere formation assay and colon cancer patient-derived organoid model.RESULTS Our results showed that DIQ significantly inhibited cell proliferation, migration, and invasion in HCT116 and HT29 cell lines. DIQ treatment induced apoptosis along with an accumulation of HCT116 and HT29 cancer cells in the sub-G1 region and an increase in reactive oxygen species in both CRC cell lines. DIQ reduced sphere-forming and self-renewal ability of colon cancer HCT116and HT29 stem/progenitor cells at sub-toxic doses of 1 μmol/L. Mechanistically, DIQ targets CSCs by downregulating the main components of stem cell-related-catenin, AKT, and ERK oncogenic signaling pathways. Potently, DIQ displayed a highly significant decrease in both the count and the size of the organoids derived from colon cancer patients as compared to control and 5-fluorouracil conditions.CONCLUSION This study is the first documentation of the molecular mechanism of the novel anticancer therapeutic DIQ via targeting CSC, a promising compound that needs further investigation.

Comparative Molecular Field Analysis(CoMFA) of Curcumin-related Compounds for Anticancer Activity

Three-dimensional （3D） quantitative structure-activity relationship （QSAR） studies of 44 curcumin-related compounds have been carried out based on our previously reported result for their anticancer activity against pancreas cancer Panc-I cells and colon cancer HT-29 cells. The established 3D-QSAR models from the comparative molecular field analysis （CoMFA） in training set showed not only significant statistical quality, but also satisfying predictive ability, with high correlation coefficient values （R12= 0.911, R22= 0.985） and cross-validation coefficient values （q2= 0.580, q22= 0.722）. Based on the CoMFA contour maps, some key structural factors responsible for anticancer activity of these series of compounds were revealed. The results provide some useful theoretical references for understanding the mechanism of action, designing new curcumin-related compounds with anticancer activity and predicting their activities prior to synthesis.

Design and Synthesis of 3-Substituedmethylenethiochroman-4-ones as Anticancer Agents

A series of 3-substituedmethylenethiochroman-4-ones was designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR, MS, IR, UV and elemental analysis. The results of their anticancer activity studies show that almost all 3-chloromethylenethiochroman-4-ones exhibit high anticancer activities and their activities are all better than reference cisplatin. Their IC50 against cancer cells is in a range of 0.80―9.17 μg/mL. Thus they could be promising candidates for anticancer drugs. However, compound 5 has no activity against cancer cells, thus chloromethylene at the 3 position of thiochroman-4-ones seems to play an important role in observed anticancer activities.

Nutritional evaluation,fatty acid analysis and anticancer properties investigation of seeds from kan-zaw,a potential diet oil and medicinal plant

Payenapara lleloneura Kurz.(Kan-zaw),an endemic medicinal plant only found in Tanintharyi Region of Myanmar,is widely used in the treatment of various cancer and different ailments.In the present research,the seeds were phytochemical investigated for their nutritional potential for their use as functional foods or novel diet oil resources.Nutritional evaluation showed that the seeds are rich in fats and carbohydrates(soluble sugars and starch).Fatty acid analyses showed that the seeds accumulate very richα-eleostearic acid(α-ESA,18:3^(Δ9 cis,11-trans),13 trans),an important conjugated fatty acid,up to more than 70% of total fatty acids.The seed oil derived from the Kan-zaw tree contains approximately 3.25% β-eleostearic acid(18:3^(Δ9 trans,11 trans,13 trans)),an unusual conjugated fatty acid that imparts a potent anticancer application and industrially important drying qualities to Kan-zaw oil.Physicochemical properties of the Kan-zaw seeds were examined;petroleum ether(60–90℃)extract of seed oils were also investigated for the saponification value,iodine value and estimation of acid value.Further,the present study investigated cytotoxic potential of ethanol,methanol,acetone,chloroform Kan-zaw seed extracts and commercial Kan-zaw oil against human cervical cancer cell line(HeLa).The Kan-zaw extracts and oil have shown significant anticancer activity on HeLa cells.

Syntheses,Structures and Vitro Anticancer Activities ofμ_2-O-andμ_2-Dimethylglyoximato-bridgedμ_3-O-Tris[di(m-fluorobenzyl)tin]Bis(dimethylglyoximate)

μ_2-O-and μ_2-dimethylglyoximato-bridged μ_3-O-tris[di（m-fluorobenzyl）tin] bis（dimethylglyoximate）（1） has been synthesized by the reaction of di（m-fluorobenzyl）tin dichloride with dimethylglyoxime. Complex 1 was characterized by means of IR,~1H NMR,elemental analysis and X-ray diffraction. It crystallizes in orthorhombic system,space group Pna21 with a = 2.22172（12）,b = 1.05566（6）,c = 2.15577（12） nm,V = 5.0561（5） nm^3,Z = 4,C_（50）H_（50）F_6N_4O_6Sn_3,Mr = 1273.01,Dc = 1. 6721 g/cm3,μ_（MoΚα） = 15.44 cm^（-1）,F（000） = 2520,R = 0.0281 and wR = 0.0683. The stabilities,orbital energies and composition characteristics of some frontier molecular orbitals of 1 have been investigated with the quantum chemistry calculation. The properties of thermogravimetric and vitro anticancer activities of the compound have been discussed.

Anticancer activity of crude acetone and water extracts of Tulbaghia violacea on human oral cancer cells

Objective: To evaluate the anticancer activity of crude acetone and water leaf extracts of Tulbaghia violacea on a human oral cancer cell line(KB).Methods: The antioxidant activity of the leaf extracts was evaluated by using the DPPH assay while the anti-proliferative activity was assessed by using the MTT assay.The morphological characteristics of apoptotic cells were examined by using the dual acridine orange/ethidium bromide staining.Flow cytometry was used to evaluate the induction of multi-caspase activity and changes in the cell cycle.Results: The acetone and water extracts exhibited antioxidant activity in a concentration dependent manner.The extracts inhibited the growth of the KB cell line with IC_(50) values of 0.2 mg/mL and 1 mg/mL, respectively for acetone and water.Morphological changes such as cell shrinkage, rounding and formation of membrane blebs were observed in the treated cells.In acridine orange/ethidium bromide staining, the number of apoptotic cells increased as the concentration of the extracts increased.The activation of multi-caspase activity in KB cells treated with Tulbaghia violacea extracts was concentration dependent, leading to cell death by apoptosis and cell cycle arrest at the G_2/M phase.Conclusions: The acetone and water extracts of Tulbaghia violacea appear to have anti-cancer activity against human oral cancer cells and need to be investigated further.

Evaluation of antiparasitic,anticancer,antimicrobial and hypoglycemic properties of organic extracts from Panamanian mangrove plants

Objective: To investigate 33 organic extracts of mangrove plants for: antiparasitic, anticancer, and antibacterial activities, as well as their ability to inhibit the activity of the α-glucosidase enzyme. Methods: Leaves from all different plant mangrove species located in five mangrove zones of the Pacific coast of Panama were collected according to standard procedures. Qualitative phytochemical analysis of the organic extracts was performed by thin layer chromatography. The antiparasitic activity against Plasmodium falciparum, Trypanosoma cruzi and Leishmania donovani, toxicity against Artemia salina, anticancer activity in MCF-7 cell line, and antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa of all organic extract were investigated according protocols stablished in our institution. Finally, the ability to inhibit the enzymatic activity of α-glucosidase was evaluated by monitoring the hydrolysis of p-nitrophenyl α-Dglucopyranoside. Results: Thirty-three different samples belonging to nine different species of vascular plants with seeds of true mangroves were collected. Triterpenoids, phenolics, and tannins were the main groups of compounds found in the sampled mangroves. Saponins, quinones, and coumarins were found in less than 50%of the samples. Laguncularia racemosa showed moderate activity against Plasmodium falciparum. None of the extracts presented anticancer activity. Rhizophora mangle exhibited potent activity against Staphylococcus aureus and Bacillus subtilis [(90.41 ±7.33)% and(96.02±6.14)% of inhibition]; Avicennia germinans and Conocarpus erectus had activity against Escherichia coli[(71.17±6.15)% and(60.60±5. 13)% of inhibition,respectively]. About 60% of the mangroves showed α-glucosidase inhibitory activity. In particular, extracts from Laguncularia racemosa, Pelliciera rhizophorae, Conocarpus erectus, Mora oleifera, and Tabebuia palustris species showed α-glucosidase inhibitory potential, with IC_(50) values of(29.45±0.29),(20.60±0.70),(730.06±3.74),(25.59±0.37), and(853.39±5.30) μg/mL, respectively. Conclusions: Panamanian mangroves are mainly a promising potential source of hypoglycemic compounds, specifically α-glucosidase inhibitors.These results highlight the therapeutic virtues of extracts from American mangrove plants.

The synthesis of boronic-imine structured compounds and identification of their anticancer, antimicrobial and antioxidant activities

Boronic acid compounds with different substituted groups were handled to synthesize various ligands encoded as B1, B2, B3, B4, BS, B6, B7 and BS. B5 and B7 were tested for the cytotoxic activity against the prostate cancer cells and it was found that the cell viability of cancer cells was decreased while most of the healthy cells could still be viable. 5 μM solutions of B5 and B7 decreased the cell viability to 33% and 44%; whereas healthy cells were 71% and 95%, respectively, after treatment. Antimicrobial properties were explored against the bacterial and fungal microorganisms with B1, B5 and BZ The inhibition zones were evaluated for all boronic structures, and the growth inhibition zones were determined in a range of 7-13 mm diameter for different microorganism species. Staphylococcus aureus was the common micro- organism that three boronic compounds with imine ligands showed the activity. Antioxidant features of B2, B3, B4, B5, B6, B7 and B8 were investigated by different processes such as Beta-carotene bleaching （BCB）, 2,2-diphenyl picryl hydrazyl （DPPH）, 2,2″-azino-bis（ 3-ethylbenzothiazoline-6-sulphonic acid） （ABTS） and CUPric reducing antioxidant capacity （CLIPRAC） methods. Significant antioxidant activity was achieved by the phenyl boronic based ligands and these compounds demonstrated as much activity as standards （α-Toc and BHT）. In addition, all structures were applied properly without any decomposition during the experiments. They were rather stable both in aqueous media and solid state.

Potential anticancer activity analysis of piscidin 5-like from Larimichthys crocea

Antitumor activity is one characteristic function of some certain antimicrobial peptides(AMPs)found in recent years.In the present study,we attempted to detect potential anticancer activity of a recombinant piscidin 5-like from Larimichthys crocea(r Lc-P5L)which owned widely antibacterial and strong antiparasitic activity in vitro.The light microscope observation indicated r Lc-P5L was of antitumor activity to He La cells,293 T cells and L929 cells.MTT assay showed the toxic sensitivity of r Lc-P5L to three tumor cell strains was 293 T>L929>He La.Scanning electron microscope(SEM)results showed r Lc-P5L behaved like a lytic peptide to cause damage on cells membrane of L929 cells by forming globular clusters,even pores at 60μmol/L,or degrading membrane to make it completely lose cytoskeleton structure at 80μmol/L;r Lc-P5L treatment also resulted in DNA degradation.Fluorescence observation results indicated r Lc-P5L could cause L929 cells at least two obvious changes:one is nucleus,nuclear chromatin condensed in the margin,nuclear volume became smaller and shrank to be out of shape,or lysed to be debris;the other is cytoskeleton,they became disordered and polarized to make cells atrophic shapes,or even lysed to be debris.In summary,r Lc-P5L owned potential anticancer activity causing membrane structure damage and genome DNA degradation.Interestingly,treatment with different concentration of r Lc-P5L seemingly caused the similar but different changes,whether it indeed gave rise to cancer cells diverse death way,the further studies should be performed,and the detailed mechanisms were still need further explored.

Self-assembly Polyrotaxanes Nanoparticles as Carriers for Anticancer Drug Methotrexate Delivery

α-Cyclodextrin/poly(ethylene glycol)(α-CD/PEG) polyrotaxane nanoparticles were prepared via a self-assembly method. Anticancer drug methotrexate(MTX) was loaded in the nanoparticles. The interaction between MTX and polyrotaxane was investigated. The formation, morphology, drug release and in vitro anticancer activity of the MTX loaded polyrotaxane nanoparticles were studied. The results show that the MTX could be efficiently absorbed on the nanoparticles, and hydrogen bonds were formed between MTX andα-CDs. The typical channel-type stacking assembly style of polyrotaxane nanoparticles was changed after MTX was loaded. The mean diameter of drug loaded polyrotaxane nanoparticles were around 200 nm and the drug loading content was as high as about 20%. Drug release profiles show that most of the loaded MTX was released within 8 hours and the cumulated release rate was as high as 98%. The blank polyrotaxane nanoparticles were nontoxicity to cells. The in vitro anticancer activity of the MTX loaded polyrotaxane nanoparticles was higher than that of free MTX.