Mechanically robust and personalized silk fibroin-magnesium composite scaffolds with water-responsive shape-memory for irregular bone regeneration.

The regeneration of critical-size bone defects, especially those with irregular shapes, remains a clinical challenge. Various biomaterials have been developed to enhance bone regeneration, but the limitations on the shape-adaptive capacity, the complexity of clinical operation, and the unsatisfied osteogenic bioactivity have greatly restricted their clinical application. In this work, we construct a mechanically robust, tailorable and water-responsive shape-memory silk fibroin/magnesium (SF/MgO) composite scaffold, which is able to quickly match irregular defects by simple trimming, thus leading to good interface integration. We demonstrate that the SF/MgO scaffold exhibits excellent mechanical stability and structure retention during the degradative process with the potential for supporting ability in defective areas. This scaffold further promotes the proliferation, adhesion and migration of osteoblasts and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. With suitable MgO content, the scaffold exhibits good histocompatibility, low foreign-body reactions (FBRs), significant ectopic mineralisation and angiogenesis. Skull defect experiments on male rats demonstrate that the cell-free SF/MgO scaffold markedly enhances bone regeneration of cranial defects. Taken together, the mechanically robust, personalised and bioactive scaffold with water-responsive shape-memory may be a promising biomaterial for clinical-size and irregular bone defect regeneration.

Composited silk fibroins ensured adhesion stability and magnetic controllability of Fe3O4-nanoparticle coating on implant for biofilm treatment.

Magnetic propulsion of nano-/micro-robots is an effective way to treat implant-associated infections by physically destroying biofilm structures to enhance antibiotic killing. However, it is hard to precisely control the propulsion in vivo. Magnetic-nanoparticle coating that can be magnetically pulled off does not need precise control, but the requirement of adhesion stability on an implant surface restricts its magnetic responsiveness. Moreover, whether the coating has been fully pulled-off or not is hard to ensure in real-time in vivo. Herein, composited silk fibroins (SFMA) are optimized to stabilize Fe3O4 nanoparticles on a titanium surface in a dry environment; while in an aqueous environment, the binding force of SFMA on titanium is significantly reduced due to hydrophilic interaction, making the coating magnetically controllable by an externally-used magnet but still stable in the absence of a magnet. The maximum working distance of the magnet can be calculated using magnetomechanical simulation in which the yielding magnetic traction force is strong enough to pull Fe3O4 nanoparticles off the surface. The pulling-off removes the biofilms that formed on the coating and enhances antibiotic killing both in vitro and in a rat sub-cutaneous implant model by up to 100 fold. This work contributes to the practical knowledge of magnetic propulsion for biofilm treatment.

Nicotinamide mononucleotide impacts HIV-1 infection by modulating immune activation in T lymphocytes and humanized mice.

BACKGROUND: HIV-1-associated immune activation drives CD4+ T cell depletion and the development of acquired immunodeficiency syndrome. We aimed to determine the role of nicotinamide mononucleotide (NMN), the direct precursor of nicotinamide adenine dinucleotide (NAD) co-enzyme, in CD4+ T cell modulation during HIV-1 infection. METHODS: We examined HIV-1 integrated DNA or transcribed RNA, intracellular p24 protein, and T cell activation markers in CD4+ T cells including in vitro HIV-1-infected cells, reactivated patient-derived cells, and in HIV-1-infected humanized mice, under NMN treatment. RNA-seq and CyTOF analyses were used for investigating the effect of NMN on CD4+ T cells. FINDINGS: We found that NMN increased the intracellular NAD amount, resulting in suppressed HIV-1 p24 production and proliferation in infected CD4+ T cells, especially in activated CD25+CD4+ T cells. NMN also inhibited CD25 expression on reactivated resting CD4+ T cells derived from cART-treated people living with HIV-1 (PLWH). In HIV-1-infected humanized mice, the frequency of CD4+ T cells was reconstituted significantly by combined cART and NMN treatment as compared with cART or NMN alone, which correlated with suppressed hyperactivation of CD4+ T cells. INTERPRETATION: Our results highlight the suppressive role of NMN in CD4+ T cell activation during HIV-1 infection. It warrants future clinical investigation of NMN as a potential treatment in combination with cART in PLWH. FUNDING: This work was supported by the Hong Kong Research Grants Council Theme-Based Research Scheme (T11-706/18-N), University Research Committee of The University of Hong Kong, the Collaborative Research with GeneHarbor (Hong Kong) Biotechnologies Limited and National Key R&D Program of China (Grant2021YFC2301900).

Development of reusable chitosan-supported nickel sulfide microspheres for environmentally friendlier and efficient bio-sorptive decontamination of mercury toxicant.

Mercury emissions from the industrial sector have become an undeniable concern for researchers due to their toxic health effects. Efforts have been made to develop green, efficient, and reliable methods for removal of mercury from wastewater. Sorption process promises fruitful results for the decontamination of cations from wastewater. Among the number of used sorbents, metal sulfides have been emerged as an appropriate material for removing toxic metals that possess good affinity due to sulfur-based active sites for Hg through "Lewis's acid-based soft-soft interactions." Herein, nickel-sulfide nanoparticles were synthesized, followed by their incorporation in chitosan microspheres. FTIR analysis confirmed the synthesis of nickel sulfide-chitosan microspheres (NiS-CMs) displaying sharp bands for multiple functional groups. XRD analysis showed that the NiS-CMs possessed a crystallite size of 42.1 nm. SEM analysis indicated the size of NiS-CMs to be 950.71 µm based on SEM micrographs. The sorption of mercury was performed using the NiS-CMs, and the results were satisfactory, with a sorption capacity of 61 mg/g at the optimized conditions of pH 5.0, 80 ppm concentration, in 60 min at 25 °C. Isothermal models and kinetics studies revealed that the process followed pseudo-second-order kinetics and the Langmuir isothermal model best fitted to experimental data. It was concluded that the NiS-CMs have emerged as the best choice for removing toxic mercury ions with a positive impact on the environment.

Design and fabrication of chitosan cross-linked bismuth sulfide nanoparticles for sequestration of mercury in river water samples.

The existence of heavy metals in ecological systems poses great threats to living organisms due to their toxicant and bio-accumulating properties. Mercury is a known toxicant with notable malignant impacts. It has long been known to cause toxic threats to the health of living organisms since the break out of Minamata disease. The turbulent expulsion of mercury-based pollutants from the industrial sector, requires a proper solution. Many attempts have been made to design a greener and more efficient route for a satisfactory removal of mercury. In the current study, bismuth sulfide nanoparticles (BiSNPs) have been synthesized via the co-precipitation method. The BiSNPs were supported with crosslinked chitosan to enhance their sorption capacity and avoid leaching. The average size of the BiSNPs was 42 nm based on SEM micrographs. The SEM analysis of the bismuth sulfide chitosan-crosslinked beads (BiS-CB) showed that the beads possessed a spherical and smooth morphology with a size of 1.02 mm. The FTIR analysis showed that the beads possessed the characteristics bands of imine groups of chitosan, bismuth, sulfur, and glycosidic linkages present in the molecules. The XRD analysis confirmed the phase crystallinity of the BiS-CB with an average crystallite size of 11 nm. The BiS-CB was employed for the sorption of mercury from water samples. The maximum sorption capacity of 65.51 mg/g was achieved at optimized conditions of pH 5, concentration 80 ppm, in 45 min at 30 °C. The mechanism studied for mercury removal showed that sorption followed the complexation mechanism according to the SHAB concept. In conclusion, the results showed that the BiS-CB sorbent exhibited an excellent sorption capacity to remove mercury.

Design strategies, surface functionalization, and environmental remediation potentialities of polymer-functionalized nanocomposites.

Inorganic nanoparticles (NPs) have a tunable shape, size, surface morphology, and unique physical properties like catalytic, magnetic, electronic, and optical capabilities. Unlike inorganic nanomaterials, organic polymers exhibit excellent stability, biocompatibility, and processability with a tailored response to external stimuli, including pH, heat, light, and degradation properties. Nano-sized assemblies derived from inorganic and polymeric NPs are combined in a functionalized composite form to import high strength and synergistically promising features not reflected in their part as a single constituent. These new properties of polymer/inorganic functionalized materials have led to emerging applications in a variety of fields, such as environmental remediation, drug delivery, and imaging. This review spotlights recent advances in the design and construction of polymer/inorganic functionalized materials with improved attributes compared to single inorganic and polymeric materials for environmental sustainability. Following an introduction, a comprehensive review of the design and potential applications of polymer/inorganic materials for removing organic pollutants and heavy metals from wastewater is presented. We have offered valuable suggestions for piloting, and scaling-up polymer functionalized nanomaterials using simple concepts. This review is wrapped up with a discussion of perspectives on future research in the field.

Dual-target platinum(IV) complexes exhibit antiproliferative activity through DNA damage and induce ER-stress-mediated apoptosis in A549 cells.

Platinum(II)-based chemotherapeutics are commonly used to treat various types of solid tumors, such as lung cancers. However, these compounds can cause serious side effects, including nephrotoxicity and ototoxicity, which affect the quality of life of patients. In our work, four novel dual target platinum(IV) complexes were designed and synthesized. In vitro results indicated that the title platinum(IV) complexes exhibited effective antitumor activities against the tested cancer cells and had lower toxicity and resistance factors than oxaliplatin and cisplatin. Further mechanistic experiments demonstrated that complex 11 accumulated in mitochondria and induced an elevation in ROS and an ER stress response via mitochondrial dysfunction. Notably, complex 11 significantly modulated the expression levels of proapoptosis proteins including cleaved-Caspase-3, Bax, and p53, and decreased the level of the prosurvival protein Bcl-2. Together, these results suggested that complex 11 might be a potential lead compound for future cancer therapy due to its potency and selectivity.

Synthesis, mechanisms of action, and toxicity of novel aminophosphonates derivatives conjugated irinotecan in vitro and in vivo as potent antitumor agents.

Twenty novel aminophosphonates derivatives (5a-5j and 6a-6j) conjugated irinotecan were synthesized through esterification reaction, and evaluated their anticancer activities using MTT assay. In vitro evaluation revealed that they displayed similar or superior cytotoxicity compared to the positive drug irinotecan against A549, MCF-7, SK-OV-3, MG-63, U2OS and multidrug-resistant (MDR) SK-OV-3/CDDP cancer cell lines. Among them, 9b displayed the most potent activity, with IC50 values of 0.92-3.23 µM against five human cancer cells, which exhibited a 5.4-19.1-fold increase in activity compared to the reference drug irinotecan, respectively. Moreover, cellular mechanism studies suggested that 9b arrested cell cycle at S stage and induced cell apoptosis along with the decrease of mitochondrial membrane potential (MMP). Interestingly, 9b significantly inhibited tumor growth in SK-OV-3 xenograft models in vivo without apparent toxicity, which was better than the positive drug irinotecan. Taken together, 9b possessed potent antitumor activity and may be a promising candidate for the potential treatment of human ovarian cancer cells.

A rapid high-performance liquid chromatography separation of a new anthocyanin from Nitraria tangutorum.

In this work, a rapid high-performance liquid chromatography method was developed to efficiently purify anthocyanin from Nitraria tangutorum based on reversed-phase column. A new anthocyanin was purified from N. tangutorum and elucidated on the basis of extensive spectroscopic analysis, including one- and two-dimensional nuclear magnetic resonance, as well as high-resolution mass spectrometry (HR-MS) data. The new anthocyanin was elucidated as cyanidin 3-[2″-(6‴-coumaroyl)-glucosyl]-glucoside.

Synthesis and biological evaluation of novel millepachine derivative containing aminophosphonate ester species as novel anti-tubulin agents.

A new series of millepachine derivative containing aminophosphonate ester moieties were designed and synthesized, and evaluated for their anticancer activities using MTT assay. Among all the compounds, compound 9m exhibited the most potent cytotoxic activity against all tested human cancer cell lines including multidrug resistant phenotype, which inhibited cancer cell growth with IC50 values ranging from 0.85 to 3.09 µM, respectively. In addition, its low cytotoxicity toward human normal liver cells HL-7702 and sensitivity toward to doxorubicin or cisplatin-resistant cells indicated the possibility for cancer therapy. Furthermore, 9m significantly induced cell apoptosis and cell cycle arrest in G2/M phase and dramatically disrupted the microtubule organization. Moreover, a decrease in MMP, an increase in reactive oxygen species (ROS) generation and Bax/Bcl-2 ratio, accompanied by activated caspase-3 and -9, were observed in HepG-2 cells after incubation with 9m, indicating that the mitochondrial pathway was involved in the 9m-mediated apoptosis.

Dual-targeting antitumor conjugates derived from platinum(IV) prodrugs and microtubule inhibitor CA-4 significantly exhibited potent ability to overcome cisplatin resistance.

Here we report that three platinum(IV) prodrugs containing a tubulin inhibitor CA-4, as dual-targeting platinum(IV) prodrug, were synthesized and evaluated for antitumor activity using MTT assay. Among them, complex 9 exhibited the most potent antitumor activity against the tested cancer lines including cisplatin resistance cancer cells, and simultaneously displayed lower toxicity compared to cisplatin, respectively. Moreover, complex 9, in which was conjugated to an inhibitor of tubulin at one axial position of platinum(IV) complex, could effectively enter the cancer cells, and significantly induce cell apoptosis and arrest the cell cycle in A549 cells at G2/M stage, and dramatically disrupt the microtubule organization. In addition, mechanism studies suggested that complex 9 significantly induced reactive oxygen species (ROS) generation and decreased mitochondrial trans-membrane potential (MMP) in A549 cells, and effectively induced activation of caspases triggering apoptotic signaling through mitochondrial dependent apoptosis pathways.

American Ginseng Attenuates Colitis-Associated Colon Carcinogenesis in Mice: Impact on Gut Microbiota and Metabolomics.

Inflammatory bowel disease is a risk factor for colorectal cancer initiation and development. In this study, the effects of American ginseng on chemically induced colitis and colon carcinogenesis were evaluated using an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. During the acute phase on day 15, the oral administration of ginseng (15 and 30 mg/kg/day) significantly suppressed AOM/DSS-induced colitis, as demonstrated by the disease activity index and colon tissue histology. During the chronic phase in week 13, AOM/DSS-induced tumor multiplicity was significantly suppressed by ginseng. Ginseng significantly attenuated the increase of inflammatory cytokines, such as IL1α, IL1ß, IL6, G-CSF, and GM-CSF. Serum metabolomics data in the PCA plots showed good separation between the AOM/DSS model and ginseng-treated mice, and the most important endogenous metabolite changes were identified. The 16S rRNA data showed that after AOM/DSS, the microbiome community in the model group was obviously changed, and ginseng inhibited these changes. Fecal metabolomics analysis supported these findings. In conclusion, oral ginseng significantly decreased AOM/DSS-induced colitis and colon carcinogenesis by inhibiting inflammatory cytokines and restoring the metabolomics and microbiota profiles accordingly. Selective endogenous small molecules could be used as biomarkers to elucidate the effects of ginseng treatment. Cancer Prev Res; 9(10); 803-11. ©2016 AACR.

Palmatine from Mahonia bealei attenuates gut tumorigenesis in ApcMin/+ mice via inhibition of inflammatory cytokines.

Mahonia bealei is a Chinese folk medicine used to treat various ailments, in particular gastrointestinal inflammation­related illnesses, and palmatine is one of its active constituents. In this study, ApcMin/+ mice, a genetically engineered model, were used to investigate the effects of palmatine on the initiation and progression of gut inflammation and tumorigenesis enhanced by a high­fat diet. The in vitro antiproliferation and anti­inflammation effects of palmatine were evaluated on HT­29 and SW­480 human colorectal cancer cell lines. The concentration­related antiproliferative effects of palmatine on both cell lines (P<0.01) were observed. Palmatine significantly inhibited lipopolysaccharide­induced increase in cytokine interleukin (IL)­8 levels in the HT­29 cells (P<0.01). In the in vivo studies with ApcMin/+ mice, after 10 or 20 mg/kg/day oral palmatine treatment, tumor numbers were significantly reduced in the small intestine and colon in a dose­dependent manner (P<0.01 compared with the model group). The results were supported by tumor distribution data, body weight changes and organ index. The effect on survival was also dose­dependent. Both the low­ and high­dose palmatine treatments significantly increased the life span of the mice (P<0.01). The gut histology from the model group showed a prominent adenomatous change along with inflammatory lesions. With palmatine treatment, however, the dysplastic changes were greatly reduced in the small intestine and colon tissue. Reverse transcription­quantitative polymerase chain reaction analysis of interleukin (IL)­1α, IL1­ß, IL­8, granulocyte­colony stimulating factor and granulocyte macrophage colony­stimulating factor in the gut tissue showed that these inflammatory cytokines were reduced significantly following treatment (all P<0.01); serum cytokine levels were also decreased. Data suggests that palmatine has a clinical value in colorectal cancer therapeutics, and this action is likely linked to the inhibition of inflammatory cytokines.

Characterization of a novel purified polysaccharide from the flesh of Cipangopaludina chinensis.

The purpose of this paper was to investigate the characterization of a novel polysaccharide from the flesh of Cipangopaludina chinensis, named CCPSn. The results found CCPSn was a white powder, readily soluble in hot water and slightly soluble in water. CCPSn was a homopolysaccharide composed of D-glucose (D-Glc) with molecular weight of 91.1 kDa. Based on analysis of UV-visible, FT-IR, periodic acid oxidation, Smith degradation, methylation, GM-MS and NMR, the structure of CCPSn was elucidated as follows: the backbone was composed of (1 → 3) linked α-D-Glc. The branches, consisting of a single (1 → 3) linked α-D-Glc units and terminal α-D-Glc-4-O-SO3(-), were attached to the main chain at C-4 positions. The degree of branching was calculated to be about 16.73%. The C-1 of terminal α-D-Glc-4-O-SO3(-) was linked to O-3 of (1 → 3) linked α-D-Glc in the branches. In addition, the results indicated CCPSn was a sulfated polysaccharide with the sulfate radical content of 9.12%.

Antitumor Activity of Total Flavonoids from Daphne genkwa in Colorectal Cancer.

Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to investigate the anticancer effects of total flavonoids in D. genkwa (TFDG) in vitro and in vivo. HT-29 and SW-480 human colorectal cancer cells were cultured to investigate the anticancer activity of TFDG. In addition, the Apc(Min/+) mouse model was applied in the in vivo experiment. Results of the cell experiment revealed that TFDG possessed significant inhibitory effects on HT-29 and SW-480 human colorectal cancer cells (both p < 0.01). Furthermore, our in vivo data showed that after treatment with TFDG, there was a significant increase in life span (both p < 0.01) and tumor numbers were reduced in the colon (both p < 0.01), which was supported by the data of tumor distribution, body weight changes and organ index. Our results also indicated that expressions of interleukin (IL)-1α, IL-1ß, IL-6, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in gut tissue were downregulated by treatments of TFDG, and immunity cytokine secretions in the serum were regulated after oral administration of TFDG. Taken together, these findings suggested that TFDG has a potential clinical utility in colorectal cancer therapeutics, and TFDG's action is likely linked to its ability to regulate immune function and inhibit the production of inflammatory cytokines.

Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in Apc(Min/+) Mice.

American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered Apc(Min/+) mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the Apc(Min/+) mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in Apc(Min/+) mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the Apc(Min/+) induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms.

American ginseng significantly reduced the progression of high-fat-diet-enhanced colon carcinogenesis in Apc (Min/+) mice.

BACKGROUND: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West. METHODS: A genetically engineered Apc (Min/+) mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. RESULTS: After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-1α (IL-1α), IL-1ß, IL-6, tumor necrosis factor-α, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). CONCLUSION: Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.

Protopanaxadiol, an active ginseng metabolite, significantly enhances the effects of fluorouracil on colon cancer.

In this study, we evaluated the effects of protopanaxadiol (PPD), a gut microbiome induced ginseng metabolite, in increasing the anticancer effects of a chemotherapeutic agent fluorouracil (5-FU) on colorectal cancer. An in vitro HCT-116 colorectal cancer cell proliferation test was conducted to observe the effects of PPD, 5-FU and their co-administration and the related mechanisms of action. Then, an in vivo xenografted athymic mouse model was used to confirm the in vitro data. Our results showed that the human gut microbiome converted ginsenoside compound K to PPD as a metabolite. PPD and 5-FU significantly inhibited HCT-116 cell proliferation in a concentration-dependent manner (both p<0.01), and the effects of 5-FU were very significantly enhanced by combined treatment with PPD (p<0.01). Cell cycle evaluation demonstrated that 5-FU markedly induced the cancer cell S phase arrest, while PPD increased arrest in G1 phase. Compared to the control, 5-FU and PPD increased apoptosis, and their co-administration significantly increased the number of apoptotic cells (p<0.01). Using bioluminescence imaging, in vivo data revealed that 5-FU significantly reduced the tumor growth up to Day 20 (p<0.05). PPD and 5-FU co-administration very significantly reduced the tumor size in a dose-related manner (p<0.01 compared to the 5-FU alone). The quantification of the tumor size and weight changes for 43 days supported the in vivo imaging data. Our results demonstrated that the co-administration of PPD and 5-FU significantly inhibited the tumor growth, indicating that PPD significantly enhanced the anticancer action of 5-FU, a commonly used chemotherapeutic agent. PPD may have a clinical value in 5-FU's cancer therapeutics.

Cycloartan-24-ene-1α,2α,3ß-triol, a cycloartane-type triterpenoid from the resinous exudates of Commiphora myrrha, induces apoptosis in human prostatic cancer PC-3 cells.

Plant-derived antitumor drugs are currently used in chemotherapy. Cycloartane triterpenoids have shown a cytotoxic effect on human prostate cancer cells. The aim of the present study was to isolate a cycloartane triterpenoid from Commiphora myrrha and evaluate its anticancer potential. Cycloartan-24-ene-1α,2α,3ß-triol (MY-1) was isolated from Commiphora myrrha, and its structure was determined through 1H and 13C nuclear magnetic resonance spectroscopy. The cytotoxic and apoptotic effects of MY-1 on human prostatic cancer PC-3 cells were estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis and terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) staining assay, and the expression of apoptotic-related proteins were evaluated by western blotting. MY-1 showed cytotoxic activity on PC-3 cells in a concentration-dependent manner with an IC50 value of 9.6 µM at 24 h. MY-1 induced cell cycle arrest and apoptosis. Western blot analysis revealed that MY-1 regulated the expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), p53 and caspase-3 in the PC-3 cells. These findings indicate that MY-1 exerts significantly pro-apoptotic activity against human hormone-independent prostatic cancer and support MY-1 as a potential anticancer drug.

American ginseng attenuates azoxymethane/dextran sodium sulfate-induced colon carcinogenesis in mice.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. METHODS: In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. RESULTS: AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. CONCLUSION: AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.