Closed-Loop Microbial Fuel Cell Control System Designed for Online Monitoring of TOC Dynamic Characteristics in Public Swimming Pool.

Total organic carbon (TOC) in the water of public swimming pools (PSPs) must be monitored online for public health. In order to address the shortcomings of conventional microbial fuel cell biosensor (MFC-biosensor), an innovative biosensor with peculiar closed-loop structure was developed for online monitoring of TOC in PSPs. Its design was based on experimental data, model identification, cybernetics, and digital and real-time simulation. The outcomes of the digital simulation demonstrated that the closed-loop MFC control system possesses the desired structure with a pair of dominant complex-conjugate closed-loop poles (-15.47 ± 7.73j), and the real-time simulation showed that its controller output signals can automatically and precisely track the variation in TOC concentration in PSP water with the desired dynamic response performances; for example, mean delay time was 0.06 h, rise time was 0.12 h, peak time was 0.18 h, maximum overshoot was 7.39%, settling time was 0.22 h, and best fit 0.98. The proposed principle and method of the closed-loop MFC-biosensor control system in the article can also be applied for online monitoring of other substances in water, such as heavy metal ions, chemical toxicants, and so forth, and lay a theoretical foundation for MFC-based online monitoring substances in an aquatic environment.

Enhanced anaerobic digestion of post-hydrothermal liquefaction wastewater: Bio-methane production, carbon distribution and microbial metabolism.

Hydrothermal liquefaction (HTL) is a cost-effective and environment-friendly technology for using biomass to produce bio-crude oil. The critical challenge of HTL is its complicated aqueous product containing high concentrations of organics and diverse toxicants. This paper reports the continuous anaerobic digestion of raw and zeolite-adsorbed Chlorella HTL wastewater using up-flow anaerobic sludge bed reactors. The bio-methane production capacity, total carbon distribution and microbial response were investigated. The anaerobic process was severely suppressed when more than 20% raw wastewater was fed; while it showed essentially improved performance till 60% pre-treated wastewater was added. Produced methane contained 17.3% of the total carbon in feedstock, which was comparable with the value (16.7%) when 25% of raw wastewater was added. The metagenomic analysis revealed distinct microbial community structures in different stages and feedstock shifts. The abundance of functional genes was consistent with anaerobic digester performance.

Water recycle system in an artificial closed ecosystem - Lunar Palace 1: Treatment performance and microbial evolution.

Water recycle systems have important implications to realize material circulation in biological regeneration life support systems, which is of significance for long-term space missions and future planetary base. Based on membrane biological activated carbon reactor (MBAR) technologies, the 'Lunar Palace 365' experiment established various treatment processes for condensate wastewater, domestic wastewater, urine, and used nutrient solutions. The 370-day operation data showed the CODMn index of purified condensate wastewater decreased to 0.74 ± 0.15 mg/L, which met the standards for drinking water quality. The average removal rate of organic contaminants in domestic wastewater by the MBAR was 85.7% ± 10.2%, and this MBAR also had a stable nitrification performance with effluent NO3--N concentrations fluctuating from 145.57 mg/L to 328.59 mg/L. Moreover, the purification of urine achieved the conversion of urea-N to NH4+-N and thus the partial recovery of nitrogen. 16S rDNA sequencing results revealed the evolution of microbial diversity and composition during the long-term operation. Meiothermus, Rhodanobacter, and Ochrobactrum were the dominant microorganisms in various MBARs.

MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH.

This study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH.

Oridonin interferes with simple steatosis of liver cells by regulating autophagy.

Oridonin has significant liver-protective effects, but its effect on liver steatosis has not been reported. We investigated the effects of oridonin on liver steatosis by cell cultures. The optimal experimental concentration of oridonin was determined through cytotoxicity experiments. A simple steatosis liver cell model was induced using free fatty acids (FFA). After adding oridonin to the FFA-induced cell model for 24 h, the lipid droplets and triglyceride (TG) content in the cells were measured by Oil Red O staining and TG kits. The expressions of autophagy-related markers (cyclin dependent kinases inhibitor 1a (p21), Beclin-1, microtubule-associated protein light chain 3 (LC3)-I and LC3-II, protein kinase B (AKT), phosphorylated-AKT (p-AKT), AMP-activated protein kinase (AMPK), and phosphorylated-AMPK (p-AMPK)) were detected by Western blot. Based on the results, the cell model was further treated by autophagy inhibitor 3-methyladenine (3-MA) to determine the degree of steatosis and the expressions of autophagy-related factors. Oridonin at a concentration higher than 10 µmol/L caused cytotoxicity to the cells. Adding 10 µmol/L oridonin to the FFA-induced cell model effectively reduced lipid droplets and TG content in the cells. Oridonin up-regulated p21, Beclin-1 and LC3-II expressions, but down-regulated those of p62 and LC3-I. Also, oridonin increased the ratios of LC3-II/LC3-I and p-AMPK/AMPK, but reduced that of p-AKT/AKT. With the addition of 3-MA, the effect of oridonin on reducing steatosis was partially reversed, and the autophagy was inhibited. This study found that oridonin can activate autophagy, thereby preventing simple steatosis of liver cells.

AMPK/mTOR/ULK1 Axis-Mediated Pathway Participates in Apoptosis and Autophagy Induction by Oridonin in Colon Cancer DLD-1 Cells.

BACKGROUND: Oridonin has been demonstrated to exert strong antitumor activities in various types of human cancers. Our previous study established that oridonin induced the apoptosis of and exerted an inhibitory effect on colon cancer cells in vitro and in vivo. However, the mechanisms behind the antitumor effects of oridonin on colorectal cancer are not clearly known. This study explored whether autophagy was involved in antitumorigenesis effects caused by the usage of oridonin in colon cancer and examined whether the AMPK/mTOR/ULK1 signaling pathway was involved in this process. METHODS: Cell viability was determined using CCK-8 assay. The distribution of cell apoptosis was evaluated using flow cytometry. RT-PCR and Western blotting analysis were conducted to identify the key target genes and proteins involved in the AMPK/mTOR cascade. AMPK siRNA was used to disturb AMPK expression. A DLD-1 cell orthotopic transplantation tumor model was established to explore the anti-cancer effects in vivo. RESULTS: Oridonin exhibited a suppressive effect on DLD-1 cells in a concentration- and time-dependent manner. Additionally, in a dose-dependent manner, oridonin induced cell apoptosis via inducing the protein expression levels of cleaved caspase-3, cleaved PARP and stimulated autophagy by increasing protein expression levels of Becin1, LC3-II, decreasing protein expression levels of LC3-I, p62, which were respectively attenuated and elevated by autophagy inhibitor 3-MA. Furthermore, oridonin upregulated the expression level of p-AMPK and downregulated the expression levels of p-mTOR, p-ULK1 in the DLD-1 cells in a dose-dependent manner. Moreover, knockdown of AMPK by a specific siRNA reversed the expression levels of proteins involved in the AMPK/mTOR pathway, autophagy and apoptosis. In addition, outcomes from the in vivo experiments also showed that oridonin treatment significantly repressed tumorigenic growth of DLD-1 cells without any side effects, which was accompanied by the upregulation of p-AMPK, LC3-II, active caspase-3 protein expression levels and the downregulation of p-mTOR and p-ULK1 protein expression levels. CONCLUSION: This study demonstrated that oridonin induced apoptosis and autophagy of colon cancer DLD-1 cells via regulating the AMPK/mTOR/ULK1 pathway, which indicated that oridonin may be used as a novel therapeutic intervention for patients with colorectal cancer.

Effect of solid waste fermentation substrate on wheat (Triticum aestivum L.) growth in closed artificial ecosystem.

Bioregenerative Life Support System (BLSS) is a closed artificial ecosystem and could provide oxygen, food, water and other substrates for long-term deep space survival. The treatment and recycle of the solid waste are crucial and rate-limiting steps in BLSS, and it's reported that the solid waste such as the inedible plants and human feces could be fermented aerobically and then reused as fertilizer for growing plants in BLSS, which may be an effective way to improve the solid waste recycling rate. However, the recycling performance and the effect on the system need to be evaluated. In this study, the fermented and decomposed solid waste product from the 365d BLSS experiment with human involved in Lunar Palace 1 was utilized, and was added to the Hoagland nutrient solution as a supplementary fertilizer in the weight proportion of 5% and 10%, respectively, for the cultivation of wheat (Group-5% and Group-10%). Then, the effects on wheat germination, morphology, photosynthesis, biomass, the conductivity of the cultured substrates and microorganisms were detected and compared with those of the CK group cultured using only Hoagland nutrient solution. The results showed that this planting method had no inhibitory effect on the wheat germination, root length and yield, and might even promote the vegetative growth of wheat in terms of Vigor index, plant height, leaf area and net photosynthesis rate to some extent. The added solid waste fermentation substrate as well as the planting environment in Lunar Palace 1 both had significant influences on the rhizosphere microorganisms of wheat. The bacteria diversity was more abundant than fungi at phylum level, and the relative abundance varied along with the wheat growth period. The relative abundance of the cellulose degrading microorganisms including Actinobacteria and Ascomycota increased in Group-5% and Group-10% compared with CK group along with the growth of wheat. Moreover, the proper reuse of the fermentation substrate could reduce the use of inorganic salts by 9.8%-11.9% and save 40L•m - 2 of water for wheat cultivation. This research has considerable application significance in future deep space exploration.

Semi-continuous fermentation of solid waste in closed artificial ecosystem: Microbial diversity, function genes evaluation.

Bioregenerative Life Support System (BLSS) is a closed artificial ecosystem and could provide oxygen, food, water and other substances for space survival. Solid waste treatment is a key rate-limiting step in BLSS. In this study, solid wastes including wheat straw, human and yellow mealworm feces were disposed in a semi-continuous bio-convertor for 105 days in a ground-based experimental BLSS platform (Lunar Palace 1). Solid wastes at different periods were sampled and the microbial community variation, functional genes and metabolic pathways were analyzed. The results showed phyla Firmicutes, Bacteroidetes and Proteobacteria predominated in all samples. While microbial community structures at genus level were significantly different, indicating selective enrichment during the 105-day process. The abundance of functional gene related to carbohydrate transport and metabolism was predicted higher on 45-day and 70-day. The metabolic pathway analysis revealed the degradation mechanisms and provided evidence for metabolic regulation.

Oridonin enhances the anti-tumor activity of gemcitabine towards pancreatic cancer by stimulating Bax- and Smac-dependent apoptosis.

BACKGROUND: Oridonin has been shown to exhibit potent anti-tumor activity, but the exact mechanisms underlying this activity remains unclear. Here, we investigated whether oridonin could synergistically enhance the activity of gemcitabine against BxPC-3 pancreatic cancer cells. METHODS: CCK-8 assays were conducted to determine cell viability. The cellular morphology was observed under light microscope and compared with normal cell. Apoptotic cells were quantified by flow cytometry. RT-PCR, Western blot analysis and immunohistochemical methods were employed to analyze related-gene and protein expression. A xenograft tumor model was conducted whereby BxPC-3 cells were introduced into nude mice to detect anti-tumor effects in vivo. RESULTS: In vitro, oridonin inhibited the proliferation of BxPC-3 and Panc-1 cells cells in a concentration and time dependent manner. In addition, oridonin dose-dependently induced Panc-1 cellular morphology changes. Besides, In BxPC-3 cells oridonin potentiated gemcitabine-induced apoptosis. oridonin induced Bax translocation from cytosolic to mitochondrial compartments. This was accompanied by the release of the apoptogenic protein Smac and inhibition of its downstream target XIAP. These effects were further enhanced by combined treatment with oridonin and gemcitabine. In vivo, both oridonin alone and in combination with gemcitabine significantly suppressed tumor growth in a Bax- and Smac-dependent manner. CONCLUSIONS: Oridonin can potentiate the effects of gemcitabine through Bax- and Smac-dependent mitochondrial signaling pathways in BxPC-3 pancreatic cancer cells. Therefore, oridonin has the potential to be used clinically in the treatment of pancreatic cancer.

Wnt/ß-catenin signaling pathway is involved in induction of apoptosis by oridonin in colon cancer COLO205 cells.

BACKGROUND: Oridonin has been demonstrated to have anticancer effect on all kinds of cancer cells and it has shown anti-tumor activity in some tumors partially via the inactivation of Wnt/ß-catenin signaling pathway. The study investigated the anticancer effect of oridonin on colon carcinoma cell line COLO205 and explored underlying mechanism. METHODS: Cell Counting Kit-8 (CCK-8) assay was performed to assess cell viability. Flow cytometry was performed to analyze the apoptosis. The key target genes and proteins involved in Wnt/ß-catenin pathway were detected by quantitative polymerase chain reaction (qPCR) and Western blotting. The xenograft tumor model of colon cancer COLO205 cell was introduced to detect anti-tumor effects in vivo. Transferase-mediated dUTP nick end labeling (TUNEL) assay was adopted to test the apoptotic cells in the tumor tissues. RESULTS: Oridonin inhibited the proliferation of colon cancer COLO205 cells in a dose-dependent and time-dependent manner. Oridonin induced apoptosis by increasing the cleavage of caspases in vitro. Furthermore, the expression levels of ß-catenin and its downstream targets, including c-myc, cyclinD1 and survivin were significantly reduced. Nevertheless the knockdown of ß-catenin by specific small interfering RNA (siRNA) could augment the anti-proliferative and pro-apoptotic effects by oridonin in COLO205 cells. Meanwhile, oridonin also increased protein expression level of glycogen synthase kinase 3ß (GSK3ß) and decreased the phosphorylation level of GSK3ß. In vivo, oridonin treatment significantly suppressed tumor growth of COLO205 cell xenografts, and which was accompanied by the restrain of Wnt/ß-catenin pathway. CONCLUSIONS: Our present study demonstrated that the growth inhibition and apoptosis induction in colon cancer COLO205 cells by oridonin could be partially mediated through discontinuing Wnt/ß-catenin signaling pathway.

Improved methane production and energy recovery of post-hydrothermal liquefaction waste water via integration of zeolite adsorption and anaerobic digestion.

Hydrothermal liquefaction (HTL) is a promising technology for converting organic wastes into bio-crude oil, with organic-rich post-hydrothermal liquefaction wastewater (PHWW) as by-product. In this study, zeolite adsorption and anaerobic digestion (AD) were integrated to improve the methane production and energy recovery of PHWW from Chlorella 1067. A statistical design for maximum toxicants removal by zeolite was applied before AD process. Zeolite could mitigate the inhibition associated to compounds such as ammonia, N-heterocyclic compounds, etc. in PHWW and thereby shortening the lag phase and increasing methane production by 32-117% compared with that without zeolite adsorption. Zeolite adsorption also increased energy recovery efficiency (up to 70.5%) for this integrated system. Integration of HTL and AD brought higher energetic return from feedstock via oil and biomethane production, which may offer insight into industrial application of microalgae biomass in the circular economy. In addition, carbon and nitrogen flow for the integrated process was determined.

Low-dose ionizing radiation limitations to seed germination: Results from a model linking physiological characteristics and developmental-dynamics simulation strategy.

There is much uncertainty about the risks of seed germination after repeated or protracted environmental low-dose ionizing radiation exposure. The purpose of this study is to explore the influence mechanism of low-dose ionizing radiation on wheat seed germination using a model linking physiological characteristics and developmental-dynamics simulation. A low-dose ionizing radiation environment simulator was built to investigate wheat (Triticum aestivum L.) seeds germination process and then a kinetic model expressing the relationship between wheat seed germination dynamics and low-dose ionizing radiation intensity variations was developed by experimental data, plant physiology, relevant hypotheses and system dynamics, and sufficiently validated and accredited by computer simulation. Germination percentages were showing no differences in response to different dose rates. However, root and shoot lengths were reduced significantly. Plasma governing equations were set up and the finite element analysis demonstrated H2O, CO2, O2 as well as the seed physiological responses to the low-dose ionizing radiation. The kinetic model was highly valid, and simultaneously the related influence mechanism of low-dose ionizing radiation on wheat seed germination proposed in the modeling process was also adequately verified. Collectively these data demonstrate that low-dose ionizing radiation has an important effect on absorbing water, consuming O2 and releasing CO2, which means the risk for embryo and endosperm development was higher.

Emodin enhances the demethylation by 5-Aza-CdR of pancreatic cancer cell tumor-suppressor genes P16, RASSF1A and ppENK.

5-Aza-2'-deoxycytidine (5-Aza-CdR) is currently acknowledged as a demethylation drug, and causes a certain degree of demethylation in a variety of cancer cells, including pancreatic cancer cells. Emodin, a traditional Chinese medicine (TCM), is an effective monomer extracted from rhubarb and has been reported to exhibit antitumor activity in different manners in pancreatic cancer. In the present study, we examined whether emodin caused demethylation and increased the demethylation of three tumor-suppressor genes P16, RASSF1A and ppENK with a high degree of methylation in pancreatic cancer when combined with 5-Aza-CdR. Our research showed that emodin inhibited the growth of pancreatic cancer Panc-1 cells in a dose- and time-dependent manner. Dot-blot results showed that emodin combined with 5-Aza-CdR significantly suppressed the expression of genome 5mC in PANC-1 cells. In order to verify the effect of methylation, methylation-specific PCR (MSP) and bisulfite genomic sequencing PCR (BSP) combined with TA were selected for the cloning and sequencing. Results of MSP and BSP confirmed that emodin caused faint demethylation, and 5-Aza-CdR had a certain degree of demethylation. When emodin was combined with 5-Aza-CdR, the demethylation was more significant. At the same time, fluorescent quantitative PCR and western blot analysis results confirmed that when emodin was combined with 5-Aza-CdR, the expression levels of P16, RASSF1A and ppENK were increased more significantly compared to either treatment alone. In contrast, the expression levels of DNA methyltransferase 1 (DNMT1) and DNMT3a were more significantly reduced with the combination treatment than the control or either agent alone, further proving that emodin in combination with 5-Aza-CdR enhanced the demethylation effect of 5-Aza-CdR by reducing the expression of methyltransferases. In conclusion, the present study confirmed that emodin in combination with 5-Aza-CdR enhanced the demethylation by 5-Aza-CdR of tumor-suppressor genes p16, RASSF1A and ppENK by reducing the expression of methyltransferases DNMT1 and DNMT3a.

Effects of emodin on the demethylation of tumor-suppressor genes in pancreatic cancer PANC-1 cells.

Emodin, a natural anthraquinone derivative isolated from Rheum palmatum, has been reported to inhibit the growth of pancreatic cancer cells through different modes of action; yet, the detailed mechanism remains unclear. In the present study, we hypothesized that emodin exerts its antitumor effect by participating in the regulation of the DNA methylation level. Our research showed that emodin inhibited the growth of pancreatic cancer PANC-1 cells in a dose- and time-dependent manner. Dot-blot results showed that 40 µM emodin significantly inhibited genomic 5 mC expression in the PANC-1 cells, and mRNA-Seq showed that different concentrations of emodin could alter the gene expression profile in the PANC-1 cells. BSP confirmed that the methylation levels of P16, RASSF1A and ppENK were decreased, while concomitantly the unmethylated status was increased. RT-PCR and western blotting results confirmed that the low expression or absence of expression of mRNA and protein in the PANC-1 cells was re-expressed following treatment with emodin. In conclusion, our study for the first time suggests that emodin inhibits pancreatic cancer cell growth, which may be related to the demethylation of tumor-suppressor genes. The related mechanism may be through the inhibition of methyltransferase expression.

Enhancement of the effects of gemcitabine against pancreatic cancer by oridonin via the mitochondrial caspase-dependent signaling pathway.

Gemcitabine is a first­line chemotherapeutic agent used in the treatment of pancreatic cancer; however resistance of the disease to the drug often develops over time. Agents that can either enhance the effects of gemcitabine, or help to overcome the chemoresistance to the drug are needed for the successful treatment of pancreatic cancer. Oridonin is one such agent which is safe and multi­targeted and has previously been shown to induce apoptosis in other tumor cells, through mitochondrial signaling pathways. The aims of the present study were to evaluate whether oridonin may enhance the effects of gemcitabine on pancreatic cancer in vitro and to investigate the possible mechanisms of this enhancement. In vitro studies have previously shown that oridonin can inhibit the proliferation of the Panc­1 pancreatic cancer cell line, and potentiate gemcitabine­induced apoptosis, which was shown to be associated with cell cycle arrest in the G1 phase. Western blot and quantitative polymerase chain reaction analyses demonstrated that the expression levels of the anti­apoptotic gene Bcl­2 and the Bcl­2/Bax ratio in the oridonin and the oridonin plus gemcitabine groups were significantly downregulated as compared with the gemcitabine treatment and control groups. The expression levels of pro­apoptotic genes Bax, cytochrome c (cyt c), and caspase­3 and ­9 in the oridonin and the combination groups were significantly upregulated as compared with the other two groups. The results suggested that oridonin improved the anti­tumor effects of gemcitabine through the enhancement of gemcitabine­induced apoptosis.This mechanism may be through the downregulation of Bcl­2 expression and the upregulation of Bax expression, resulting in the reduction of the Bcl­2/Bax ratio. These effects may promote the release of cyt c from the mitochondria into the cytoplasm thus triggering the mitochondrial apoptosis signaling pathway. Furthermore, caspase­3 and ­9 were shown to be activated as a result of the induction of apoptosis.

Oridonin induces apoptosis in SW1990 pancreatic cancer cells via p53- and caspase-dependent induction of p38 MAPK.

Oridonin, an active component isolated from Rabdosia rubescens, has been reported to exhibit antitumor effects. In the present study, we evaluated the antitumor activity and the mechanisms of action of oridonin in pancreatic cancer. Oridonin treatment significantly induced apoptotic cell death in SW1990 pancreatic cancer cells in a dose-dependent manner. Additionally, cell apoptosis was markedly inhibited by PFT α (pifithrin α), a p53-specific inhibitor, which was applied to evaluate the function of p53, showing that p53 was responsible for the cytotoxity of oridonin. Moreover, oridonin increased the expression of p-p53 with a concomitant increase in p21 in the SW1990 cells. Following treatment with mitogen-activated protein kinase (MAPK) inhibitors, PD98059 (ERK inhibitor), SP600125 (JNK inhibitor) and SB203580 (p38 inhibitor), the cytotoxity of oridonin was not influenced by JNK (SP600125) and ERK (PD98059), but these effects were opposite to the cytotoxity of oridonin observed with SP203580 treatment. These findings confirmed that orodonin-induced apoptosis was p38-dependent, but JNK- and ERK-independent. Furthermore, the activation of the p38 kinase promoted the activation of p53 and its downstream target p21, and further caused caspase-9 and -3 activation, as demonstrated by evidence showing that the p38 inhibitor SB203580 not only blocked the phosphorylation of p38 but also reduced the activation of p53, p21 and caspase-9 and -3. Collectively, these results suggest that p53-dependent and caspase-dependent induction of p38 MAPK directly participates in apoptosis induced by oridonin.

The distinct mechanisms of the antitumor activity of emodin in different types of cancer (Review).

Emodin, a tyrosine kinase inhibitor, is a natural anthraquinone derivative found in the roots and rhizomes of numerous plants. The inhibitory effect of emodin on mammalian cell cycle modulation in specific oncogene-overexpressing cells has formed the basis for using this compound as an anticancer drug. Previous reviews have summarized the antitumor properties of emodin. However, the specific molecular mechanisms of emodin-mediated tumor inhibition have not been completely elucidated over the last 5 years. Recently, there has been great progress in the preclinical study of the anticancer mechanisms of emodin. Our recent study revealed that emodin has therapeutic effects on pancreatic cancer through various antitumor mechanisms. Notably, the therapeutic efficacy of emodin in combination with chemotherapy was found to be higher than the comparable single chemotherapeutic regime, and the combination therapy also exhibited fewer side-effects. Despite these encouraging results, further investigation is warranted as emodin has been shown to modulate one or more key regulators of cancer growth. This review provides an overview of the distinct mechanisms of anticancer action of emodin in different body systems identified over the past 5 years. These new breakthrough findings may have important implications for targeted cancer therapy and for the future clinical use of emodin.

Emodin sensitizes the gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine via downregulation of NF-κB and its regulated targets.

The aim of this study was to evaluate whether emodin can overcome the chemoresistance of the gemcitabine-resistant cancer cell line (Bxpc-3/Gem) in vitro. The cell line Bxpc-3/Gem was derived from the human pancreatic cancer cell line Bxpc-3. We found that Bxpc-3/Gem cells were characterized by a series of morphological changes with a resistance index of 43.51 comparing with the parental cell line. Emodin reduced Bxpc-3/Gem cell proliferation in a dose-dependent manner. Emodin and gemcitabine combination treatments resulted in decreased cell proliferation and increased apoptosis in Bxpc-3/Gem cells. In addition, combination treatments resulted in downregulation of gene and protein expression of MDR-1 (P-gp), NF-κB, XIAP, survivin, as well as inhibition of NF-κB activity and P-gp function. These observations suggest that emodin may sensitize the pancreatic cancer gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine therapy via inhibition of survival signaling.

Antitumor activity of emodin against pancreatic cancer depends on its dual role: promotion of apoptosis and suppression of angiogenesis.

BACKGROUND: Emodin has been showed to induce apoptosis of pancreatic cancer cells and inhibit tumor growth in our previous studies. This study was designed to investigate whether emodin could inhibit the angiogenesis of pancreatic cancer tissues and its mechanism. METHODOLOGY/PRINCIPAL FINDING: In accordance with our previous study, emodin inhibited pancreatic cancer cell growth, induced apoptosis, and enhanced the anti-tumor effect of gemcitabine on pancreatic caner cells in vitro and in vivo by inhibiting the activity of NF-κB. Here, for the first time, we demonstrated that emodin inhibited tumor angiogenesis in vitro and in implanted pancreatic cancer tissues, decreased the expression of angiogenesis-associated factors (NF-κB and its regulated factors VEGF, MMP-2, MMP-9, and eNOS), and reduced eNOS phosphorylation, as evidenced by both immunohistochemistry and western blot analysis of implanted tumors. In addition, we found that emodin had no effect on VEGFR expression in vivo. CONCLUSIONS/SIGNIFICANCE: Our results suggested that emodin has potential anti-tumor effect on pancreatic cancer via its dual role in the promotion of apoptosis and suppression of angiogenesis, probably through regulating the expression of NF-κB and NF-κB-regulated angiogenesis-associated factors.

Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic cancer xenograft model in vivo via inhibition of inhibitors of apoptosis.

Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. As members of apoptosis inhibitors, Survivin and XIAP play an important role in chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and emodin enhanced antitumor efficacy in pancreatic cancer. The application of the combination therapy triggered significantly higher frequency of pancreatic cancer cell apoptosis. Our research demonstrated that the combination of emodin and gemcitabine resulted in significantly reduced tumor volumes compared to gemcitabine or emodin treatment alone. Immunohistochemistry and western immunoblot analyses showed that Survivin and XIAP expression were downregulated in emodin and the combination groups compared to the other two groups. Reverse transcriptase polymerase chain reaction analyses showed that Survivin and XIAP mRNA expression in emodin and the combination groups were downregulated significantly compared to the other two groups. Furthermore, the expression of the nuclear transcription factor κB (NF-κB) protein and NF-κB mRNA were downregulated in the emodin and the combination groups. DNA-binding activity of NF-κB was inhibited in emodin and combination groups compared to the other groups. This study suggests that emodin potentiates the antitumor effects of gemcitabine in PANC-1 cell xenografts via promotion of apoptosis and IAP suppression.