Sulfated Galactans from Agarophytes: Review of Extraction Methods, Structural Features, and Biological Activities.

Agarophytes are important seaweeds of the Rhodophyta type, which have been highly exploited for industrial use as sources of a widely consumed polysaccharide of agar. In addition to that, sulfated galactans (SGs) from agarophytes, which consist of various functional sulfate groups, have attracted the attention of scientists in current studies. SGs possess various biological activities, such as anti-tumor, anticoagulant, anti-inflammatory, antioxidant, anti-obesity, anti-diabetic, anti-microbial, anti-diarrhea, and gut microbiota regulation properties. Meanwhile, the taxonomy, ecological factors, i.e., environmental factors, and harvest period, as well as preparation methods, i.e., the pretreatment, extraction, and purification conditions, have been found to influence the chemical compositions and fine structures of SGs, which have, further, been shown to have an impact on their biological activities. However, the gaps in the knowledge of the properties of SGs due to the above complex factors have hindered their industrial application. The aim of this paper is to collect and systematically review the scientific evidence about SGs and, thus, to pave the way for broader and otherwise valuable industrial applications of agarophytes for human enterprise. In the future, this harvested biomass could be sustainably used not only as a source of agar production but also as natural materials in functional food and pharmaceutical industries.

Bioactivities of the Popular Edible Brown Seaweed Sargassum fusiforme: A Review.

Sargassum fusiforme has a wide range of active constituents (such as polysaccharides, sterols, polyphenols, terpenes, amino acids, trace elements, etc.) and is an economically important brown algae with a long history. In recent years, S. fusiforme has been intensively studied and has attracted wide attention in the fields of agriculture, environment, medicine, and functional food. In this review, we reviewed the current research status of S. fusiforme at home and abroad over the past decade by searching Web of science, Google Scholar, and other databases, and structurally analyzed the active components of S. fusiforme, and on this basis, we focused on summarizing the cutting-edge research and scientific issues on the role of various active substances in S. fusiforme in exerting antioxidant, anti-inflammatory, antitumor, antidiabetic, immunomodulatory, antiviral antibacterial, and anticoagulant effects. The mechanisms by which different substances exert active effects were further summarized by exploring different experimental models and are shown visually. It provides a reference to promote further development and comprehensive utilization of S. fusiforme resources.

Anti-Melanogenesis and Anti-Photoaging Effects of the Sulfated Polysaccharides Isolated from the Brown Seaweed Padina boryana.

Sulfated polysaccharides isolated from seaweeds are thought of as ideal ingredients in the pharmaceutical, nutraceutical, and cosmetics industries. Our previous study isolated and characterized sulfated polysaccharides from Padina boryana. The sulfated polysaccharides of Padina boryana (PBP) were extracted, and the antioxidant activity of PBP was evaluated. The results indicate that PBP possesses antioxidant effects and potential in the cosmetic industry. To further investigate the potential of PBP in cosmetics, the photoprotective and anti-melanogenesis effects of PBP were evaluated. The anti-melanogenesis test results display that PBP reduced the melanin content in the murine melanoma cells stimulated by alpha melanocyte-stimulating hormone from 203.7% to 183.64%, 144.63%, and 127.57% at concentrations of 25 µg/mL, 50 µg/mL, and 100 µg/mL, respectively. The anti-photodamage test results showed that PBP significantly protected skin cells against UVB-stimulated photodamage. PBP suppressed human epidermal keratinocyte (HaCaT cell) death by inhibiting apoptosis and reducing the level of intracellular reactive oxygen species. The intracellular reactive oxygen species level of HaCaT cells irradiated by UVB was reduced from 192.67% to 181.22%, 170.25%, and 160.48% by 25 µg/mL, 50 µg/mL, and 100 µg/mL PBP, respectively. In addition, PBP remarkably reduced UVB-induced human dermal fibroblast damage by suppressing oxidative damage, inhibiting collagen degradation, and attenuating inflammatory responses. These results indicate that PBP possesses photoprotective and anti-melanogenesis activities and suggest that PBP is a potential ingredient in the cosmetic industry.

Impact of Monascus purpureus fermentation on antioxidant activity, free amino acid profiles and flavor properties of kelp (Saccharina japonica).

This study evaluated the efficacy of Monascus purpureus fermentation on Saccharina japonica (SJ). Healthy substances and antioxidant activity of fermented SJ (FSJ) were determined. Results showed that fermentation caused the release of phenolic compounds and flavonoids, which resulted in the enhancement of antioxidant activity. Essential amino acids and γ-aminobutyric acid also greatly accumulated in FSJ. Sensory evaluation and gas chromatography-ion mobility spectrometry (GC-IMS) were used to evaluate flavor properties of FSJ. A lexicon consisted of 24 descriptors was established for SJ and FSJ, of which 14 descriptors were regarded as odor attributes. A total of 46 volatile compounds were identified by GC-IMS and showed positive correlation with odor attributes. Fifteen volatile compounds were screened as key compounds, tricarboxylic acid cycle, embden-meyerhof-parnas and amino acid catabolism were main formation metabolisms of them. Advanced properties of FSJ indicated that fermentation is a promising approach for the production of SJ food.

Anti-inflammatory effect of fucoidan isolated from fermented Sargassum fusiforme in in vitro and in vivo models.

Fucoidans possess potent anti-inflammatory effects. In the present study, the anti-inflammatory effect of the fucoidan (SFF-PS-F5) isolated from fermented Sargassum fusiforme was evaluated in vitro in RAW 264.7 macrophages and in vivo in zebrafish. The in vitro test results demonstrate that SFF-PS-F5 effectively inhibited nitric oxide (NO) production induced by lipopolysaccharides (LPS) in RAW 264.7 cells. SFF-PS-F5 effectively and concentration-dependently improved the viability of LPS-stimulated RAW 264.7 cells, and reduced the level of prostaglandin E2, interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6. Further results display that these effects were actioned by suppressing the expression of inducible nitric oxide synthase and cyclooxygenase-2 via regulating the nuclear factor kappa-B signaling pathway. The in vivo test results indicate that SFF-PS-F5 remarkably reduced reactive oxygen species, cell death, and NO levels in LPS-treated zebrafish. These results indicate that SFF-PS-F5 could inhibit both in vitro and in vivo inflammatory responses and suggest it is a functional ingredient in the functional food and cosmetic industries.

Anti-Inflammatory Effect of Sulfated Polysaccharides Isolated from Codium fragile In Vitro in RAW 264.7 Macrophages and In Vivo in Zebrafish.

In this study, the anti-inflammatory activity of sulfated polysaccharides isolated from the green seaweed Codium fragile (CFCE-PS) was investigated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results demonstrated that CFCE-PS significantly increased the viability of LPS-induced RAW 264.7 cells in a concentration-dependent manner. CFCE-PS remarkably and concentration-dependently reduced the levels of inflammatory molecules including prostaglandin E2, nitric oxide (NO), interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6 in LPS-stimulated RAW 264.7 cells. In addition, in vivo test results indicated that CFCE-PS effectively reduced reactive oxygen species, cell death, and NO levels in LPS-stimulated zebrafish. Thus, these results indicate that CFCE-PS possesses in vitro and in vivo anti-inflammatory activities and suggest it is a potential ingredient in the functional food and pharmaceutical industries.

Single-Cell Identification, Drug Susceptibility Test, and Whole-genome Sequencing of Helicobacter pylori Directly from Gastric Biopsy by Clinical Antimicrobial Susceptibility Test Ramanometry.

BACKGROUND: The battle against Helicobacter pylori (H. pylori) infections demands fast, reliable, and sensitive methods for pathogen identification (ID), antimicrobial susceptibility tests (ASTs) based on metabolic response, and genome-wide mutation profiling that reveals resistance mechanisms. METHODS: Here we introduce Clinical Antimicrobial Susceptibility Test Ramanometry for H. pylori (CAST-R-HP), and its validation with clinical samples. This method performs rapid ID, metabolism inhibition-based AST, and high-quality whole-genome sequencing for cells of targeted resistance phenotype, all at precisely 1-cell resolution and directly from biopsy samples. RESULTS: In CAST-R-HP, automated acquisition and machine learning of single-cell Raman spectra (SCRS) enable distinguishing individual H. pylori cells directly from a biopsy sample, with 98.5 ± 0.27% accuracy in ID. Moreover, by adding a 48- to72-h D2O feeding and drug exposure step prior to SCRS acquisition, CAST-R-HP reports AST for levofloxacin and clarithromycin with 100% accuracy, based on metabolic inhibition level. Furthermore, CAST-R-HP supports rapid sorting, low-bias DNA amplification, and full genome sequencing of single H. pylori cells with the SCRS defined, targeted drug-susceptibility phenotype, via Raman-activated gravity-driven cell encapsulation and sequencing. The genome-wide mutation map (maximum 99.70% coverage), at precisely 1-cell resolution, not only elucidates the drug-susceptibility phenotypes but also unveils their underlying molecular mechanisms. CONCLUSION: The culture independency, shorter turnaround time, high resolution, and comprehensive information output suggest that CAST-R-HP is a powerful tool for diagnosing and treating H. pylori infections.

In Vitro and In Vivo Anti-Inflammatory Effects of Sulfated Polysaccharides Isolated from the Edible Brown Seaweed, Sargassum fulvellum.

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.

Agar oligosaccharides: A review of preparation, structures, bioactivities and application.

Agar, a gelatinous polysaccharide which is in the cell wall of many red algae, is widely used as food and gelling agent. Agar oligosaccharides (AOs), the hydrolysate of agar, show much more kinds of bio-activities because of its lower molecular weight, better water solubility and higher absorption efficiency. It is indicated that AOs with different structure and degree of polymerization, i.e. series of agaro-oligosaccharides and neoagaro-oligosaccharides, can be obtained under different preparation conditions. In addition, the biological activities of AOs are diversely and closely correlated to the composition and structure. This review aims to comprehensively summarize the preparation, structural characteristics and bio-activities of AOs, so as to provide a reference for applications of AOs as marine natural products in pharmacological, cosmetics and nutraceutical fields.

A Sulfated Polysaccharide from Saccharina japonica Suppresses LPS-Induced Inflammation Both in a Macrophage Cell Model via Blocking MAPK/NF-κB Signal Pathways In Vitro and a Zebrafish Model of Embryos and Larvae In Vivo.

Inflammation is a complicated host-protective response to stimuli and toxic conditions, and is considered as a double-edged sword. A sulfated Saccharinajaponica polysaccharide (LJPS) with a sulfate content of 9.07% showed significant inhibitory effects against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophage cells and zebrafish. Its chemical and structural properties were investigated via HPLC, GC, FTIR, and NMR spectroscopy. In vitro experiments demonstrated that LJPS significantly inhibited the generation of nitric oxide (NO) and prostaglandin E2 (PGE2) via the downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and suppressed pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1ß production via the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signal pathways in LPS-induced RAW 264.7 cells. Moreover, LJPS showed strong protective effects against LPS-induced inflammatory responses in zebrafish, increasing the survival rate, reducing the heart rate and yolk sac edema size, and inhibiting cell death and the production of intracellular reactive oxygen species (ROS) and NO. Its convenience for large-scale production and significant anti-inflammatory activity indicated the potential application of LJPS in functional foods, cosmetics, and pharmaceutical industries.

Protective Effect of a Fucose-Rich Fucoidan Isolated from Saccharina japonica against Ultraviolet B-Induced Photodamage In Vitro in Human Keratinocytes and In Vivo in Zebrafish.

A fucose-rich fucoidan was purified from brown seaweed Saccharina japonica, of which the UVB protective effect was investigated in vitro in keratinocytes of HaCaT cells and in vivo in zebrafish. The intracellular reactive oxygen species levels and the viability of UVB-irradiated HaCaT cells were determined. The results indicate that the purified fucoidan significantly reduced the intracellular reactive oxygen species levels and improved the viability of UVB-irradiated HaCaT cells. Furthermore, the purified fucoidan remarkably decreased the apoptosis by regulating the expressions of Bax/Bcl-xL and cleaved caspase-3 in UVB-irradiated HaCaT cells in a dose-dependent manner. In addition, the in vivo UV protective effect of the purified fucoidan was investigated using a zebrafish model. It significantly reduced the intracellular reactive oxygen species level, the cell death, the NO production, and the lipid peroxidation in UVB-irradiated zebrafish in a dose-dependent manner. These results suggest that purified fucoidan has a great potential to be developed as a natural anti-UVB agent applied in the cosmetic industry.

Selenocystine inhibits JEG-3 cell growth in vitro and in vivo by triggering oxidative damage-mediated S-phase arrest and apoptosis.

BACKGROUND: Selenocystine (SeC) is a nutritionally available selenoamino acid presenting novel anticancer potential against human cancers. However, neither the effects nor mechanism of SeC against choriocarcinoma growth has been clarified yet. This study investigated the anticancer effects and mechanism of SeC against JEG-3 human choriocarcinoma growth in vitro and in vivo. MATERIALS AND METHODS: The in vitro anticancer efficiency was evaluated with cell viability, apoptosis, and oxidative stress. JEG-3 cell viability was determined with 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell cycle distribution and apoptosis were examined by flow cytometric analysis. Oxidative damage was detected with immunofluorescence and western blotting. The in vivo anticancer efficiency was evaluated in immunodeficient mouse model of choriocarcinoma. The mechanism was also investigated. RESULTS: SeC dose and time dependently inhibited the viability of JEG-3 cells in vitro. The result of flow cytometry (FCM) analysis showed that obvious S-phase arrest and cell apoptosis were initiated by SeC in JEG-3 cells, which was further convinced by the decreased levels of cyclin A, poly-ADP-ribose polymerase cleavage, and activation of caspase-3,-7, and-9. In addition, SeC resulted in significant generation of reactive oxygen species (ROS) and superoxide anion, followed by the activation of DNA damage. However, SeC-induced oxidative damage and apoptosis were effectively blocked after ROS inhibition. Further investigation indicated that SeC effectively suppressed JEG-3 choriocarcinoma tumor xenograft growth in vivo. The mechanism may be the induction of cell apoptosis and oxidative damage through inhibiting cell proliferation (Ki-67) and angiogenesis (CD-31). CONCLUSIONS: Our findings supported that human choriocarcinoma growth could be inhibited by SeC in vitro and in vivo through triggering oxidative damage-mediated S-phase arrest and apoptosis. Thus, SeC may be promising in the treatment of human choriocarcinoma.

Selenocysteine antagonizes oxygen glucose deprivation-induced damage to hippocampal neurons.

Designing and/or searching for novel antioxidants against oxygen glucose deprivation (OGD)-induced oxidative damage represents an effective strategy for the treatment of human ischemic stroke. Selenium is an essential trace element, which is beneficial in the chemoprevention and chemotherapy of cerebral ischemic stroke. The underlying mechanisms for its therapeutic effects, however, are not well documented. Selenocysteine (SeC) is a selenium-containing amino acid with neuroprotective potential. Studies have shown that SeC can reduce irradiation-induced DNA apoptosis by reducing DNA damage. In this study, the in vitro protective potential and mechanism of action of SeC against OGD-induced apoptosis and neurotoxicity were evaluated in HT22 mouse hippocampal neurons. We cultured HT22 cells in a glucose-free medium containing 2 mM Na2S4O2, which formed an OGD environment, for 90 minutes. Findings from MTT, flow cytometry and TUNEL staining showed obvious cytotoxicity and apoptosis in HT22 cells in the OGD condition. The activation of Caspase-7 and Caspase-9 further revealed that OGD-induced apoptosis of HT22 cells was mainly achieved by triggering a mitochondrial-mediated pathway. Moreover, the OGD condition also induced serious DNA damage through the accumulation of reactive oxygen species and superoxide anions. However, SeC pre-treatment for 6 hours effectively inhibited OGD-induced cytotoxicity and apoptosis in HT22 cells by inhibiting reactive oxygen species-mediated oxidative damage. Our findings provide evidence that SeC has the potential to suppress OGD-induced oxidative damage and apoptosis in hippocampal neurons.

Selenium-Containing Protein From Selenium-Enriched Spirulina platensis Attenuates Cisplatin-Induced Apoptosis in MC3T3-E1 Mouse Preosteoblast by Inhibiting Mitochondrial Dysfunction and ROS-Mediated Oxidative Damage.

Accumulated evidences have verified that cancer chemotherapy may increase the risk of osteoporosis and severely affected the life quality. Osteoclasts hyperactivation was commonly accepted as the major pathogenesis of osteoporosis. However, the role of osteoblasts dysfunction in osteoporosis was little investigated. Our previous study has confirmed that selenium-containing protein from selenium-enriched Spirulina platensis (Se-SP) exhibited enhanced hepatoprotective potential through inhibiting oxidative damage. Herein, the protective effect of Se-SP against cisplatin-induced osteoblasts dysfunction in MC3T3-E1 mouse preosteoblast was investigated, and the underlying mechanism was evaluated. The results indicated that cisplatin dramatically decreased cell viability of preosteoblast by triggering mitochondria-mediated apoptosis pathway. Cisplatin treatment also caused mitochondrial dysfunction and reactive oxide species (ROS)-mediated oxidative damage. However, Se-SP pre-treatment effectively prevented MC3T3-E1 cells from cisplatin-induced mitochondrial dysfunction by balancing Bcl-2 family expression and regulating the opening of mitochondrial permeability transition pore (MPTP), attenuated cisplatin-induced oxidative damage through inhibiting the overproduction of ROS and superoxide anion, and eventually reversed cisplating-induced early and late apoptosis by inhibiting PARP cleavage and caspases activation. Our findings validated that Se-SP as a promising Se species could be a highly effective way in the chemoprevention and chemotherapy of oxidative damage-mediated bone diseases.

Antiangiogenic properties of caudatin in vitro and in vivo by suppression of VEGF­VEGFR2­AKT/FAK signal axis.

Tumor angiogenesis provides essential nutrients and oxygen to the tumor microenvironment, which is important in tumor growth, progression and metastasis. Inhibition of tumor angiogenesis represents one of the most promising strategies in tumor therapy. The authors previously demonstrated that caudatin, one species of C­21 steroidal from Cynanchum auriculatum (C. auriculatum), effectively inhibits human glioma growth in vitro and in vivo through triggering cell cycle arrest and apoptosis. However, little information regarding the antiangiogenic properties of caudatin in human glioma is available. Based on the author's previous study, the antiangiogenic effect of caudatin against human glioma was explored, and the underlying mechanism was investigated. The results suggested that caudatin treatment significantly inhibited HUVEC human umbilical vein endothelial cell proliferation, blocked the HUVECs migration, invasion and capillary­like tube formation by disturbing the vascular endothelial growth factor (VEGF)­VEGFR2­protein kinase B (AKT)/focal adhesion kinase (FAK) signal axis. Notably, caudatin treatment abolished the glioma cell growth by suppression of the in vivo angiogenesis, which involved FAK and AKT dephosphorylation and inhibition of VEGF expression. The findings validated the antiangiogenic potential of caudatin in hunting human glioma.

Selenocysteine induces apoptosis in human glioma cells: evidence for TrxR1-targeted inhibition and signaling crosstalk.

Thioredoxin reductase (TrxR) as a selenium (Se)-containing antioxidase plays key role in regulating intracellular redox status. Selenocystine (SeC) a natural available Se-containing amino acid showed novel anticancer potential through triggering oxidative damage-mediated apoptosis. However, whether TrxR-mediated oxidative damage was involved in SeC-induced apoptosis in human glioma cells has not been elucidated yet. Herein, SeC-induced human glioma cell apoptosis was detected in vitro, accompanied by PARP cleavage, caspases activation and DNA fragmentation. Mechanically, SeC caused mitochondrial dysfunction and imbalance of Bcl-2 family expression. SeC treatment also triggered ROS-mediated DNA damage and disturbed the MAPKs and AKT pathways. However, inhibition of ROS overproduction effectively attenuated SeC-induced oxidative damage and apoptosis, and normalized the expression of MAPKs and AKT pathways, indicating the significance of ROS in SeC-induced apoptosis. Importantly, U251 human glioma xenograft growth in nude mice was significantly inhibited in vivo. Further investigation revealed that SeC-induced oxidative damage was achieved by TrxR1-targeted inhibition in vitro and in vivo. Our findings validated the potential of SeC to inhibit human glioma growth by oxidative damage-mediated apoptosis through triggering TrxR1-targeted inhibition.

Extraction and Identification of Phlorotannins from the Brown Alga, Sargassum fusiforme (Harvey) Setchell.

Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene), which are unique compounds from marine brown algae. In our present study, a procedure for extraction and enrichment of phlorotannins from S. fusiforme with highly antioxidant potentials was established. After comparison of different extraction methods, the optimal extraction conditions were established as follows. The freeze-dried seaweed powder was extracted with 30% ethanol-water solvent with a solid/liquid ratio of 1:5 at temperature of 25 °C for 30 min. After extraction, the phlorotannins were fractioned by different solvents, among which the ethyl acetate fraction exhibited both the highest total phlorotannin content (88.48 ± 0.30 mg PGE/100 mg extract) and the highest antioxidant activities. The extracts obtained from these locations were further purified and characterized using a modified UHPLC-QQQ-MS method. Compounds with 42 different molecular weights were detected and tentatively identified, among which the fuhalol-type phlorotannins were the dominant compounds, followed by phlorethols and fucophlorethols with diverse degree of polymerization. Eckol-type phlorotannins including some newly discovered carmalol derivatives were detected in Sargassum species for the first time. Our study not only described the complex phlorotannins composition in S. fusiforme, but also highlighted the challenges involved in structural elucidation of these compounds.

Reversal of Beta-Amyloid-Induced Neurotoxicity in PC12 Cells by Curcumin, the Important Role of ROS-Mediated Signaling and ERK Pathway.

Progressive accumulation of beta-amyloid (Aß) will form the senile plaques and cause oxidative damage and neuronal cell death, which was accepted as the major pathological mechanism to the Alzheimer's disease (AD). Hence, inhibition of Aß-induced oxidative damage and neuronal cell apoptosis by agents with potential antioxidant properties represents one of the most effective strategies in combating human AD. Curcumin (Cur) a natural extraction from curcuma longa has potential of pharmacological efficacy, including the benefit to antagonize Aß-induced neurotoxicity. However, the molecular mechanism remains elusive. The present study evaluated the protective effect of Cur against Aß-induced cytotoxicity and apoptosis in PC12 cells and investigated the underlying mechanism. The results showed that Cur markedly reduced Aß-induced cytotoxicity by inhibition of mitochondria-mediated apoptosis through regulation of Bcl-2 family. The PARP cleavage, caspases activation, and ROS-mediated DNA damage induced by Aß were all significantly blocked by Cur. Moreover, regulation of p38 MAPK and AKT pathways both contributed to this protective potency. Our findings suggested that Cur could effectively suppress Aß-induced cytotoxicity and apoptosis by inhibition of ROS-mediated oxidative damage and regulation of ERK pathway, which validated its therapeutic potential in chemoprevention and chemotherapy of Aß-induced neurotoxicity.

Induction of G1 Cell Cycle Arrest in Human Glioma Cells by Salinomycin Through Triggering ROS-Mediated DNA Damage In Vitro and In Vivo.

Chemotherapy has always been one of the most effective ways in combating human glioma. However, the high metastatic potential and resistance toward standard chemotherapy severely hindered the chemotherapy outcomes. Hence, searching effective chemotherapy drugs and clarifying its mechanism are of great significance. Salinomycin an antibiotic shows novel anticancer potential against several human tumors, including human glioma, but its mechanism against human glioma cells has not been fully elucidated. In the present study, we demonstrated that salinomycin treatment time- and dose-dependently inhibited U251 and U87 cells growth. Mechanically, salinomycin-induced cell growth inhibition against human glioma was mainly achieved by induction of G1-phase arrest via triggering reactive oxide species (ROS)-mediated DNA damage, as convinced by the activation of histone, p53, p21 and p27. Furthermore, inhibition of ROS accumulation effectively attenuated salinomycin-induced DNA damage and G1 cell cycle arrest, and eventually reversed salinomycin-induced cytotoxicity. Importantly, salinomycin treatment also significantly inhibited the U251 tumor xenograft growth in vivo through triggering DNA damage-mediated cell cycle arrest with involvement of inhibiting cell proliferation and angiogenesis. The results above validated the potential of salinomycin-based chemotherapy against human glioma.

Caudatin induces caspase-dependent apoptosis in human glioma cells with involvement of mitochondrial dysfunction and reactive oxygen species generation.

Caudatin as one species of C-21 steroidal from Cynanchum bungei decne displays potential anticancer activity. However, the underlying mechanisms remain elusive. In the present study, the growth suppressive effect and mechanism of caudatin on human glioma U251 and U87 cells were evaluated in vitro. The results indicated that caudatin significantly inhibited U251 and U87 cell growth in both a time- and dose-dependent manner. Flow cytometry analysis revealed that caudatin-induced cell growth inhibition was achieved by induction of cell apoptosis, as convinced by the increase of Sub-G1 peak, PARP cleavage and activation of caspase-3, caspase-7 and caspase-9. Caudatin treatment also resulted in mitochondrial dysfunction which correlated with an imbalance of Bcl-2 family members. Further investigation revealed that caudatin triggered U251 cell apoptosis by inducing reactive oxygen species (ROS) generation through disturbing the redox homeostasis. Moreover, pretreatment of caspase inhibitors apparently weakens caudatin-induced cell killing, PARP cleavage and caspase activation and eventually reverses caudatin-mediated apoptosis. Importantly, caudatin significantly inhibited U251 tumour xenografts in vivo through induction of cell apoptosis involving the inhibition of cell proliferation and angiogenesis, which further validate its value in combating human glioma in vivo. Taken together, the results described above all suggest that caudatin inhibited human glioma cell growth by induction of caspase-dependent apoptosis with involvement of mitochondrial dysfunction and ROS generation.