Anticancer Bioactivity Research Articles

Baicalin suppresses proliferation, migration, and invasion in human glioblastoma cells via Ca2+-dependent pathway.

ObjectiveBaicalin, a kind of flavonoid extracted from the dry root of Scutellaria, possesses potent anticancer bioactivities in various tumor cell lines. Accumulating evidences show that baicalin induces autophagy and apoptosis to suppress the cancer growth. Moreover, the antineoplastic role of baicalin in human glioblastoma cells remains to be uncovered.MethodsBoth U87 and U251 human glioblastoma cell lines were employed in the present study. Cell viability was tested by Cell Counting Kit-8 and colony-forming assay; Flow cytometry was employed to analyze cell apoptosis, cell cycle, and Ca2+ content. Cell immunofluorescence assays were used for analyzing terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), light chain 3 beta (LC3B), 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanineiodide (JC-1), and Ca2+ content. The protein levels were tested by Western blot. The SPSS software was used for statistical analysis.ResultsBaicalin suppressed the proliferation, migration, and invasion ability of human glioblastoma cells in a dose-dependent manner. Baicalin induced the loss of mitochondrial membrane potential and led to mitochondrial apoptosis. The maturation of microtubule-associated protein 1A/1B-LC3B indicated the activation of autophagy potentially through PI3K/Akt/mTOR pathway, and inhibition of autophagy by 3-methyladenine decreased the apoptotic cell ratio. Besides, baicalin increased the intercellular Ca2+ content; meanwhile, chelation of free Ca2+ by 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid inhibited both apoptotic and autophagy. Finally, baicalin suppressed tumor growth in vivo.ConclusionOur observations suggest that baicalin exerts cytotoxic effects on human glioblastoma cells by the autophagy-related apoptosis through Ca2+ movement to the cytosol. Furthermore, baicalin has the potential as a candidate for the treatment of glioblastoma.

Eriodictyol Attenuates LPS-Induced Neuroinflammation, Amyloidogenesis, and Cognitive Impairments via the Inhibition of NF-κB in Male C57BL/6J Mice and BV2 Microglial Cells.

Eriodictyol, a natural flavonoid mainly distributed in citrus fruits and peanut, has been well-documented with possession of excellent anti-inflammatory, antioxidant, and anticancer bioactivities. This work focus on the protective effects of eriodictyol on LPS-induced neuroinflammation, amyloidogenesis, cognitive impairment, and the potential mechanisms involved. Behavioral tests and histological examinations showed that eriodictyol significantly prevented the memory and neuronal damage triggered by LPS. Consistently, eriodictyol (100 mg/kg) reduced the formation of Aβ1-42 by 28.37 ± 16.71 pg/mL compared to the LPS group. In addition, high dose eriodictyol (100 mg/kg) also equilibrated the cholinergic system via suppressing AChE activity (0.1996 ± 0.0831 U/mgprot) and elevating ChAT activity (41.81 ± 24.72 U/g) as well as ACh level (5.093 ± 3.531 μg/mgprot) compared to the LPS group. Western blot results indicated that compared to the LPS group, eriodictyol suppressed LPS-induced glial overactivation (84.29% ± 27.21%) and regulated inflammatory mediators and cytokines by inhibiting the NF-κB and MAPK pathways. These results indicated that eriodictyol alleviated amyloidogenesis and memory impairment triggered by LPS via inhibiting TLR4, MAPKs, and PI3K/Akt, and activating Sirt1 pathways and thus blocking downstream translocation of NF-κB, which offers a potential nutritional preventive strategy for neuroinflammation diseases such as Alzheimer's disease (AD).

Correction to "Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer Bioactivity Against Colorectal Cancer".

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to “Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer Bioactivity Against Colorectal Cancer”Qi HaoQi HaoMore by Qi Hao, Yueyue ChenYueyue ChenMore by Yueyue Chen, Zehuan HuangZehuan HuangMore by Zehuan Huang, Jiang-Fei XuJiang-Fei XuMore by Jiang-Fei Xu, Zhiwei Sun*Zhiwei SunMore by Zhiwei Sun, and Xi Zhang*Xi ZhangMore by Xi Zhanghttp://orcid.org/0000-0002-4823-9120Cite this: ACS Appl. Mater. Interfaces 2018, 10, 33, 28250Publication Date (Web):August 9, 2018Publication History Published online9 August 2018Published inissue 22 August 2018https://doi.org/10.1021/acsami.8b11812Copyright © 2018 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views827Altmetric-Citations1LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (179 KB) Get e-Alerts Get e-Alerts

Bioactives in seaweeds, algae, and fungi and their role in health promotion

Seaweeds, algae, and fungi are rich sources of a myriad of bioactive compounds. In recent years, special attention has been paid to these secondary metabolites with biological activities that exist in aquatic foods and might render beneficial health effects in humans. Various antioxidant, anticancer, antidiabetic, antiobesity and antimicrobial bioactives have been isolated from seaweeds, algal and fungal species may be used as functional components in foods, food supplement, and as nutraceutical or medicine to promote human health and reduce disease risk. This review provides a cursory account of the health promoting bioactives such as sulfated polysaccharides, various polyphenols, polyunsaturated fatty acids (PUFAs), sterols, proteins and their hydrolysates, bioactive peptides, minerals, vitamins as well as pigments derived from various seaweeds, algal, and fungal species focusing on their potential application and health benefits. In addition, a brief description is provided for the extraction of such bioactives and techniques used to isolate and characterize them.

Delaying Anticancer Drug Delivery by Self-Assembly and Branching Effects of Minimalist Dendron-Drug Conjugates.

Self-assembly of a covalently-bound lipophilic drug to a dendronic scaffold for making organic nanoparticles is reported as a proof of concept in nanovectorization. A minimalist structural approach with a small PEG-dendron conjugated to paclitaxel (PTX), incorporating safe succinic and gallic acids, is efficient to provide the expected anticancer bioactivity, but also significantly retards and targets intracellular delivery of PTX in 2D and 3D lung cancer cell cultures. A branching effect of dendrons is crucial, when compared to linear PTX conjugates. Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) studies indicate the formation of stable, low-disperse nanoparticles at 10-5 m in H2 0, which could also be responsible for the biological effects. An ultrasensitive LC-MS/MS method was used for the determination of intracellular PTX concentration over time, along with the survival rates of cancer cells. Similarly, cell survival assays were successfully correlated to a 3D cell culture with spheroids for mimicking tumors, when treated with PTX conjugates. Our work opens the way to a full evaluation program required for new chemical entities.

Betulinic acid chemosensitizes breast cancer by triggering ER stress-mediated apoptosis by directly targeting GRP78

Stress-induced cellular defense machinery has a critical role in mediating cancer drug resistance, and targeting stress-related signaling has become a novel strategy to improve chemosensitivity. Betulinic acid (BA) is a naturally occurring pentacyclic triterpenoid with potent anticancer bioactivities in multiple malignancies, whereas its underlying mechanisms remain unclear. Here in, we found that BA has synergistic effects with taxol to induce breast cancer cells G2/M checkpoint arrest and apoptosis induction, but had little cytotoxicity effects on normal mammary epithelial cells. Drug affinity responsive target stability (DARTS) strategy further identified glucose-regulated protein 78 (GRP78) as the direct interacting target of BA. BA administration significantly elevated GRP78-mediated endoplasmic reticulum (ER) stress and resulted in the activation of protein kinase R-like ER kinase (PERK)/eukaryotic initiation factor 2a/CCAAT/enhancer-binding protein homologous protein apoptotic pathway. GRP78 silencing or ER stress inhibitor salubrinal administration was revealed to abolish the anticancer effects of BA, indicating the critical role of GRP78 in mediating the bioactivity of BA. Molecular docking and coimmunoprecipitation assay further demonstrated that BA might competitively bind with ATPase domain of GRP78 to interrupt its interaction with ER stress sensor PERK, thereby initiating the downstream apoptosis cascade. In vivo breast cancer xenografts finally validated the chemosensitizing effects of BA and its biofunction in activating GRP78 to trigger ER stress-mediated apoptosis. Taken together, our study not only uncovers GRP78 as a novel target underlying the chemosensitizing effects of BA, but also highlights GRP78-based targeting strategy as a promising approach to improve breast cancer prognosis.

Cytotoxic activity of Shp2 inhibitor fumosorinone in human cancer cells.

Fumosorinone (Fumos) isolated from entomogenous fungi Isaria fumosorosea exhibited selective inhibition of Src homology phosphotyrosine phosphatase 2 inhibitor (Shp2) in our previous study. The purpose of the present study was to investigate the effects of Fumos on cell cycle arrest, tumor cell migration and the in vitro antiproliferative activity of Fumos alone or in combination with the commonly used cytotoxic drugs 5-fluoracil (5-FU) and p38 inhibitor SB203580. Fumos exhibited cytotoxicity against selected human cancel lines, including HeLa, MDA-MB-231 and MDA-MB-453 cell lines. Fumos exerted selective cytotoxic effects on the human cell lines. Flow cytometric and DAPI assays showed that Fumos did not induce cell apoptosis, however it induced cell cycle arrest at the G1 phase. Fumos inhibited cell migration though reducing the phosphorylation of focal adhesion kinase (FAK) at tyrosine (Tyr)861 and marginally increasing the phosphorylation of FAK at Tyr397, however, Fumos did not affect the phosphorylation of FAK at Tyr576 or Tyr925. The present study also examined the combination effect of Fumos with other chemical agents, including 5-FU and p38 inhibitor SB203580. Fumos exhibited a marked synergistic effect with these agents, particularly with 5-FU. In conclusion, Fumos showed potential anticancer bioactivity, and the combination effect of Fumos with 5-FU or with p38 inhibitor offers a more effective anticancer strategy for carcinoma treatment.

In vitro investigation of cytotoxic and antioxidative activities of Ardisia crispa against breast cancer cell lines, MCF-7 and MDA-MB-231

BackgroundArdisia crispa Thunb. D.C is used mostly in some parts of the Asian region by traditional practitioners to treat certain diseases associated with oxidative stress and inflammation including cancer and rheumatism. In Malaysia, it is popularly known as ‘Mata Ayam’ and local traditional practitioners believed that the root of the plant is therapeutically beneficial.MethodsThe cytotoxic effect of hydromethanolic extract of A. crispa and its solvents partitions (ethyl acetate and aqueous extracts) against breast cancer cells were evaluated by using MTT assay. The cells were treated with concentration of extracts ranging from 15.63 μg/mL- 1000 μg/mL for 72 h. The quantification of phenolic and flavonoid contents of the extracts were carried out to determine the relationship between of phytochemical compounds responsible for cytotoxic and antioxidative activities. The antioxidant capacity was measured by DPPH and ABTS free radical scavenging assay and expressed as milligram (mg) Trolox equivalent antioxidant capacity per 1 g (g) of tested extract.ResultsThe hydromethanolic and ethyl acetate extracts showed moderate cytotoxic effect against MCF-7 with IC50 values of 57.35 ± 19.33 μg/mL, and 54.98 ± 14.10 μg/mL, respectively but aqueous extract was inactive against MCF-7. For MDA-MB-231, hydromethanolic, ethyl acetate and aqueous extracts exhibited weak cytotoxic effects against MDA-MB-231 with IC50 values more than 100 μg/mL. The plant revealed high total phenolic content, total flavonoid and antioxidant capacity.ConclusionThe response of different type of breast cancer cell lines towards A. crispa extract and its partitions varied. Accordingly, hydromethanolic and ethyl acetate extracts appear to be more cytotoxic to oestrogen receptor (ER) positive breast cancer than oestrogen receptor (ER) negative breast cancer. However, aqueous extract appears to have poor activity to both types of breast cancer. Besides that, hydromethanolic and ethyl acetate extracts exhibit higher TPC, TFC and antioxidant capacity compared to aqueous extract. Synergistic effect of anticancer and antioxidant bioactives compounds of A. crispa plausibly contributed to the cytotoxic effects of the extract.

Aspergillus niger is a superior expression host for the production of bioactive fungal cyclodepsipeptides

BackgroundFungal cyclodepsipeptides (CDPs) are non-ribosomally synthesized peptides produced by a variety of filamentous fungi and are of interest to the pharmaceutical industry due to their anticancer, antimicrobial and anthelmintic bioactivities. However, both chemical synthesis and isolation of CDPs from their natural producers are limited due to high costs and comparatively low yields. These challenges might be overcome by heterologous expression of the respective CDP-synthesizing genes in a suitable fungal host. The well-established industrial fungus Aspergillus niger was recently genetically reprogrammed to overproduce the cyclodepsipeptide enniatin B in g/L scale, suggesting that it can generally serve as a high production strain for natural products such as CDPs. In this study, we thus aimed to determine whether other CDPs such as beauvericin and bassianolide can be produced with high titres in A. niger, and whether the generated expression strains can be used to synthesize new-to-nature CDP derivatives.ResultsThe beauvericin and bassianolide synthetases were expressed under control of the tuneable Tet-on promoter, and titres of about 350–600 mg/L for bassianolide and beauvericin were achieved when using optimized feeding conditions, respectively. These are the highest concentrations ever reported for both compounds, whether isolated from natural or heterologous expression systems. We also show that the newly established Tet-on based expression strains can be used to produce new-to-nature beauvericin derivatives by precursor directed biosynthesis, including the compounds 12-hydroxyvalerate-beauvericin and bromo-beauvericin. By feeding deuterated variants of one of the necessary precursors (d-hydroxyisovalerate), we were able to purify deuterated analogues of beauvericin and bassianolide from the respective A. niger expression strains. These deuterated compounds could potentially be used as internal standards in stable isotope dilution analyses to evaluate and quantify fungal spoilage of food and feed products.ConclusionIn this study, we show that the product portfolio of A. niger can be expanded from enniatin to other CDPs such as beauvericin and bassianolide, as well as derivatives thereof. This illustrates the capability of A. niger to produce a range of different peptide natural products in titres high enough to become industrially relevant.

Phenethyl ester and amide of Ferulic Acids: Synthesis and bioactivity against P388 Leukemia Murine Cells

Bioactivity of a compound is closely related to the molecular structure of the compound concerned, its strength being the quantitative relation of the strength of the activity of the group it possesses. The combining of moieties of the active compounds will produce more active compounds. Most phenolic compounds as well as compounds containing moiety phenethyl groups have potential activity as anticancer. Combining phenolic groups and phenethyl groups in a compound will result in compounds having strong anticancer bioactivity. This study aims to combine the feruloyl and phenethyl groups to form esters and amides by synthesize of phenethyl trans-3-(4-hydroxy-3-methoxyphenyl)acrylate (5) and trans-3-(4- hydroxy-3-methoxyphenyl)-N-phenethylacrylamide (6) from ferulic acid with phenethyl alcohol and phenethylamine, and to study their bioactivity as anticancer. The synthesis of both compounds was conducted via indirect reaction, including acetylation, chlorination, esterfication/amidation, and deacetylation. Structures of products were characterized by FTIR and NMR data, and their bioactivity assay of the compounds against P388 Leukemia Murine Cells was conducted by an MTT method. Results showed that the compound 5 was obtained as a yellow gel with the IC50 of 10.79 μg/mL (36.21 μΜ), and the compound 6 was a yellowish solid with a melting point of 118-120°C and the IC50 of 29.14 μg/mL (97.79 μΜ). These compounds were more active than the analog compounds.

Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its Anticancer Bioactivity Against Colorectal Cancer.

We have successfully demonstrated that the host-guest complex of carboxylated pillar[6]arene with oxaliplatin (OxPt) exhibits low cytotoxicity toward normal cells and displays higher anticancer bioactivity against colorectal cancer cells than OxPt itself. Owing to higher binding affinity of carboxylated pillar[6]arene with spermine (SPM) than that with OxPt, the encapsulated OxPt can be thoroughly released from its host-guest complex by the competitive replacement with SPM. This supramolecular chemotherapy works well both in vitro and in vivo for SPM-overexpressed cancers, such as colorectal cancer. Compared to OxPt itself, the anticancer bioactivity of this host-guest complex is further improved by about 20%. Such an improvement results from the combined effect of controlled release of OxPt from its host-guest complex and simultaneous consumption of SPM by carboxylated pillar[6]arene. It is anticipated that this supramolecular strategy may be extended to other clinical anticancer drugs for decreasing their severe side effects and improving their anticancer bioactivity, thus enriching the realm of supramolecular chemotherapy.

Synthesis of novel 6-substituted amino-9-(β-d-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells

New nucleoside derivatives with nitrogen substitution at the C-6 position were prepared and screened initially for their in vitro anticancer bioactivity against human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI-sulforhodamine B assay. N6-(4-trifluoromethylphenyl)piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC50 = 1–4 μM) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines. The most potent nucleosides (11, 13, 16, 18, 19, 21, 27, 28) were further screened for their cytotoxicity in hepatocellular cancer cell lines. The compound 27 demonstrated the highest cytotoxic activity against Huh7, Mahlavu and FOCUS cells (IC50 = 1, 3 and 1 μM respectively). Physicochemical properties, drug-likeness, and drug score profiles of the molecules showed that they are estimated to be orally bioavailable. The results pointed that the novel derivatives would be potential drug candidates.

Biotechnological Applications of Bioactive Peptides From Marine Sources.

This review is an overview on marine bioactive peptides with promising activities for the development of alternative drugs to fight human pathologies. In particular, we focus on potentially prolific producers of peptides in microorganisms, including sponge-associated bacteria and marine photoautotrophs such as microalgae and cyanobacteria. Microorganisms are still poorly explored for drug discovery, even if they are highly metabolically plastic and potentially amenable to culturing. This offers the possibility of obtaining a continuous source of bioactive compounds to satisfy the challenging demands of pharmaceutical industries. This review targets peptides because of the variety of potent biological activities demonstrated by these molecules, including antiviral, antimicrobial, antifungal, antioxidant, anticoagulant, antihypertensive, anticancer, antidiabetic, antiobesity, and calcium-binding bioactivities. Several of these peptides have already gained recognition as effective drug agents in recent years. We also focus on cutting-edge omic approaches for the discovery of novel compounds for pharmacological applications. With rapid depletion of natural resources, omic technologies may be the solution to efficiently produce a vast variety of novel peptides with unique pharmacological potential.

Occurrence, biological activity and metabolism of 6-shogaol.

As one of the main bioactive compounds of dried ginger, 6-shogaol has been widely used to alleviate many ailments. It is also a major pungent flavor component, and its precursor prior to dehydration is 6-gingerol, which is reported to be responsible for the pungent flavor and biological activity of fresh ginger. Structurally, gingerols including 6-gingerol have a β-hydroxyl ketone moiety and is liable to dehydrate to generate an α,β-unsaturated ketone under heat and/or acidic conditions. The conjugation of the α,β-unsaturated ketone skeleton in the chemical structure of 6-shogaol explicates its higher potency and efficacy than 6-gingerol in terms of antioxidant, anti-inflammatory, anticancer, antiemetic and other bioactivities. Research on the health benefits of 6-shogaol has been conducted and results have been reported recently; however, scientific data are scattered due to a lack of systematic collection. In addition, action mechanisms of the preventive and/or therapeutic actions of 6-shogaol remain obscurely non-collective. Herein, we review the preparations, biological activity and mechanisms, and metabolism of 6-shogaol as well as the properties of 6-shogaol metabolites.

Bufalin suppresses colorectal cancer cell growth through promoting autophagy in vivo and in vitro.

Specific groups in Asia, including the Chinese, are more susceptible to colorectal cancer (CRC). The best strategy for anticancer drug action is to induce cancer cell apoptosis and autophagy. Bufalin is a potent inducer of apoptosis in some human cancer cell lines, but bufalin has barely been evaluated in colorectal cancer cells as a potent autophagy inducing agent. The aim of this study was to investigate the roles and interactions of bufalin in autophagy and the effects of the drug on human colorectal cancer. We applied bufalin and autophagy inhibitors (CQ and 3-MA) in LoVo cells to investigate their potential anticancer bioactivity under certain concentrations of bufalin to monitor autophagy and cell proliferation in vivo and in vitro. Bufalin induced autophagy of LoVo and inhibited proliferation of LoVo cells. Bufalin inhibited the expression of autophagy-related (ATG) proteins and tumor growth in vivo. Our studies identified that bufalin could potentially be a small molecule inhibitor for cancer therapy.

Liensinine perchlorate inhibits colorectal cancer tumorigenesis by inducing mitochondrial dysfunction and apoptosis.

Colorectal cancer (CRC) is one of the most common cancers worldwide with poor survival and limited therapeutic options, and there is an urgent need to develop novel therapeutic agents with good treatment efficiency and low toxicity. This study aims to examine the anticancer bioactivity of liensinine, a constituent of Nelumbo nucifera Gaertn, in CRC and investigate the action mechanisms involved. Liensinine was found to induce apoptosis and exert a significant inhibitory effect on the proliferation and colony-forming ability of CRC cells in a dose-dependent manner without any observed cytotoxicity on normal colorectal epithelial cells. Mechanistically, our data from quantitative proteomics, western blot analysis and flow cytometry analyses demonstrated that exposure of CRC cells to liensinine caused cell cycle arrest, mitochondrial dysfunction and apoptosis, accompanied by the activation of the JNK signaling pathway. Furthermore, animal experiments showed that liensinine markedly suppressed the growth of CRC tumor xenografts in nude mice by reducing the Ki-67 proliferation index, but did not damage the vital organs of the animals. This study demonstrated for the first time that liensinine, a food-source natural product, could be a novel therapeutic strategy for treating CRC without obvious side effects.

Nature is the best source of anticancer drugs: Indexing natural products for their anticancer bioactivity.

Cancer is considered one of the primary diseases that cause morbidity and mortality in millions of people worldwide and due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. However, the traditional process of drug discovery and development is lengthy and expensive, so the application of in silico techniques and optimization algorithms in drug discovery projects can provide a solution, saving time and costs. A set of 617 approved anticancer drugs, constituting the active domain, and a set of 2,892 natural products, constituting the inactive domain, were employed to build predictive models and to index natural products for their anticancer bioactivity. Using the iterative stochastic elimination optimization technique, we obtained a highly discriminative and robust model, with an area under the curve of 0.95. Twelve natural products that scored highly as potential anticancer drug candidates are disclosed. Searching the scientific literature revealed that few of those molecules (Neoechinulin, Colchicine, and Piperolactam) have already been experimentally screened for their anticancer activity and found active. The other phytochemicals await evaluation for their anticancerous activity in wet lab.

Effect of Hydrolyzed Fucoidan from The Brown Seaweed Sargassum Binderi Sonder Towards Human Breast Cancer T47d Cell Lines

Fucoidan, a sulfated heteropolysaccharide, consists of L-fucose and sulfate ester groups as the main component. Over the past three decades, fucoidan structures and bioactivities have been widely studied. The chemical components (fucose, galactose, small monosaccharides and also the sulfate) and the molecular weights of fucoidans from different brown seaweed species produce different characteristics and structures of fucoidan. The activity of fucoidan against cancer cells has been reported to be affected strongly by their sulfate content and molecular weight. Low-molecular-weight fucoidans tend to have higher solubility and easily penetrate into cancer cells. The objective of this study was to investigate the effect of hydrolyzed of fucoidan on its anti cancer activity againts the breast cancer T47D cells. In this study, the fucoidan from the brown seaweed Sargassum binderi Sonder was extracted using 0.1 N HCl and was depolymerized by acid hydrolysis at various times and concentrations. Result showed that fucoidan hydrolyzed with 1 M trifluoroacetic acid (TFA) for 1.5 hours reached the maximum depolymerization process and resulted in the decrement of molecular weight from 785.12 kDa to 5.79 kDa as well as sulfate content from 18.63% to 8.69%. The IC50 values of fucoidan and low molecular weight fucoidan against the breast cancer T47D cells were 60.03 mg/mL and 182.34 mg/ respectively. This result indicated that the sulfate content of fucoidan probably affected its anticancer bioactivities.

Study on β-cyclodextrin-complexed nanogels with improved thermal response for anticancer drug delivery

For achievement of controllability in drug delivery, development of nanocarriers with thermal response is one of the most investigated stimulative strategies for oncological treatment. How to improve the thermosensitivity of the nanocarriers is an important factor for their successful drug delivery applications. In this study, a kind of complexed nanogels (PNACD) was developed by incorporating β-cyclodextrin (β-CD) into the nanogels of copolymers of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) during their polymerization via in situ crosslinking of N,N′-methylenebisacrylamide (MBA) as a crosslinker. The complexed PNACD nanogels displayed a significantly enhanced thermosensitivity near body temperature compared to the β-CD-free nanogels (PNA), which is probably associated with the rapid volumetric transformation during heating/cooling process due to the formation of complexed (decomplexed) structure between β-CD and PNIPAM element. The PNACD nanogels can be used for loading of an anticancer drug (doxorubicin, DOX) with an encapsulation efficiency of 54±5%. The DOX-loaded nanogels displayed pH-/thermo-dual responsivenesses in drug release, which can be effectively internalized into KB cells (a human epithelial carcinoma cell line) to exert good anticancer bioactivity. This approach may enlighten design of novel nanocarriers for delivery of drugs beyond anticancer chemotherapeutic reagents.

Polysaccharide lentinan extracted from the stipe of Lentinus edodes mushroom exerts anticancer activities through the transcriptional regulation of cell cycle progression and metastatic markers in human colon cancer cells

The edible mushroom Lentinus edodes has been shown to offer medicinal effects including antifungal, antibacterial, antiviral, antioxidant, as well as anticancer activities. Assessment of bioactivities of extracts of the mushroom indicated that the polysaccharide lentinan possesses the potential bioactivities. Currently, the stipe portion of the mushroom is mostly discarded during industrial food processing, generating a large amount of residues. The hypothesis is that the stipe as the industrial byproduct from the mushroom processing contains the similar bioactive polysaccharide that could be utilized to produce mushroom extracts for treatment of cancer. Therefore the current study was designed to examine the polysaccharide extract from the mushroom stipe and its anticancer bioactivities in human colon cancer cells. The preparation and storage methods used in the production of lentinan polysaccharide were also optimized in the study. An aqueous phase extraction method was used for the lentinan production from the stipe as well as the pileus of Lentinus edodes mushroom (LeS vs LeP). Results showed that the lentinan yield from the stipe is comparable to the pileus. WST‐1 assay indicated that at as little as 125 ug/ml, lentinan extracts from both LeS and LeP exerted inhibitory effects against cell proliferation of human colon cancer cells. Cell cycle analysis using flow cytometry indicated that the anti‐proliferative effect is partly due to the induction of cell cycle arrest at the G0/1 phase. Further analysis of gene expression showed that the cell cycle arrest induced by lentinan treatment was associated with a decrease in the mRNA level of cyclin D1 gene. This is accompanied by the reduction of transcription of oncogenes such as c‐myc and induction of gene expression for stress‐responsive pathways. Moreover, NDRG1 gene, a key regulator of cancer metastasis that was often silenced in metastatic colon cancer cells, was increased by lentinan treatment. Together, the current study demonstrates that Letinous edodes stipe is a valuable source of lentinan. Lentinan from Letinous edodes stipe extract is stable when stored under the freeze‐dried condition or at refrigeration. The anti‐proliferative effects of lentinan in colon cancer cells are the results of cell cycle arrest that was induced by the inhibition of cyclin production, combined with the induction of cellular stress‐responsive pathways as well as the transcription of metastasis suppressor genes.Support or Funding InformationThe research is supported by the Office of International Programs of College of ACES at University of Illinois at Urbana‐Champaign and USDA HATCH fund.