Rice bran arabinoxylan compound as a natural product for cancer treatment - an evidence-based assessment of the effects and mechanisms.

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.

Plant-derived extracellular vesicles as a promising anti-tumor approach: A comprehensive assessment of effectiveness, safety, and mechanisms.

BACKGROUND: Plant-derived extracellular vesicles (PDEs) are expected to be a compelling alternative for cancer treatment due to their low cytotoxicity, low immunogenicity, high yield, and potential anti-tumor efficacy. Despite the significant advantages of PDEs, the reliable evidence for PDEs as promising anti-tumor approach remains unsystematic and insufficient. Some challenges remain for the clinical application and large-scale industrial production of PDEs. PURPOSE: Through systematic evaluation and meta-analysis, the objective was to provide scientific, systematic and reliable preclinical evidence to support the clinical use of PDEs in cancer therapy. METHODS: The search for relevant literature, conducted up to March 2024, encompassed various databases including Web of Science, the Cochrane Library, Embase, PubMed, CNKI, Wanfang Data, and the China Science and Technology Journal Database. The SYRCLE´s risk of bias tool was used to assess the methodological quality of the animal studies. For overall effect analysis and subgroup analysis, RevMan 5.4 and Stata 12.0 were utilized. RESULTS: The analysis incorporated a total of 38 articles, comprising 29 in vivo studies and 9 in vitro studies. Meta-analysis indicated that PDEs significantly reduced cancer cell activity and induced apoptosis, reduced tumor volume and tumor weight when used as therapeutic agents, as well as exhibited synergistic anti-cancer via combination therapy. Additionally, PDEs-drugs exerted stronger inhibition of tumor volume compared to the free drug or commercial liposome-drugs. Their therapeutic effects were closely related to regulating tumor cell biological behavior and remodeling the tumor microenvironment. The safety was associated with administration route of PDEs, oral administration was currently preferred until more in-depth studies on the safety of other methods are conducted. CONCLUSIONS: The meta-analysis revealed that PDEs have systematic and reliable preclinical evidence in preclinical studies of cancer therapy, and their efficacy and certain safety could support the clinical application of PDEs in cancer therapy. Of course, further researches are required for large-scale industrial production to meet the needs of clinical applications.

Untargeted metabolomics-based identification of bioactive compounds from Mangifera indica L. seed extracts in drug discovery through molecular docking and assessment of their anticancer potential.

BACKGROUND: Mangifera indica L. (mango), a medicinal plant rich in biologically active compounds, has potential to be used in disease-preventing and health-promoting products. The present investigation reveals and uncovers bioactive metabolites with remarkable therapeutic efficiency from mango (family: Anacardiaceae) seeds. RESULTS: Biological activity was determined by antimicrobial, antioxidant and anticancer assays, and metabolite profiling was performed on gas chromatography coupled to quadrupole time-of-flight mass spectrometry (GC-QTOF-MS) and liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) platforms. Validation of active metabolites was carried out by in silico molecular docking (Molinspiration Cheminformatics Server and PASS). Extracted and identified metabolites were screened; 54 compounds associated with various groups were selected for the in silico interaction study. CONCLUSIONS: Molecular docking revealed lead molecules with a potential binding energy score, efficacy and stable modulation with a selected protein domain. Investigation, directed by in vitro and in silico analysis, confirms mango seeds as an excellent source of potential metabolites as a therapeutic agent. © 2024 Society of Chemical Industry.

In Vitro Assessment of the Cytotoxic and Antiproliferative Profile of Natural Preparations Containing Bergamot, Orange and Clove Essential Oils.

Medicinal plants and essential oils (EOs), in particular, were intensively studied in recent years as viable alternatives for antiproliferative chemical synthetic agents. In the same lines, the present study focuses on investigating the effects of natural preparations (emulsions) based on EOs obtained from Citrus bergamia Risso (bergamot-BEO), Citrus sinensis Osbeck (orange-OEO), and Syzygium aromaticum Merill et L. M. Perry (clove-CEO) on different healthy (human immortalized keratinocytes-HaCaT and primary human gingival fibroblasts-HGF) and human tumor cell lines (human melanoma-A375 and oral squamous carcinoma-SCC-4) in terms of the cells' viability and cellular morphology. The obtained results indicate that the CEO emulsion (ECEO) induced a dose-dependent cytotoxic in both healthy (HaCaT and HGF) and tumor (A375 and SCC-4) cells. OEO emulsion (EOEO) increased cell viability percentage both for HaCaT and A375 cells and had an antiproliferative effect at the highest concentration in HGF and SCC-4 cells. BEO emulsion (EBEO) decreased the viability percentage of SCC-4 tumor cells. By associating OEO with CEO as a binary mixture in an emulsified formulation, the inhibition of tumor cell viability increases. The E(BEO/OEO) binary emulsion induced an antiproliferative effect on oral health and tumor cells, with a minimal effect on skin cells. The non-invasive tests performed to verify the safety of the test compound's emulsions at skin level indicated that these compounds do not significantly modify the physiological skin parameters and can be considered safe for human skin.

Assessment of the Cytotoxic Activity of Triphala: A Semisolid Traditional Formulation on HepG2 Cancer Cell Line.

Cancer chemotherapies may result in resistance, and therefore, contemporary treatments including natural products may find an increasing consideration. As per Persian medicine (PM), many natural products have been used for malignant and chronic diseases. Triphala, with a combination of Terminalia chebula Retz., Terminalia bellirica Retz., Phyllanthus emblica L., and honey, is a multi-ingredient traditional formulation attributed to anticancer activities in PM. This study is aimed at evaluating the cytotoxic activity of this preparation on HepG2, the human liver cancer cell line. Hydroalcoholic extracts were prepared from the formulation and its components. Compared with the control and Cisplatin, the extracts were tested using MTT assay at different concentrations. All concentrations of the preparation, as well as Cisplatin, were effective significantly against HepG2 cells. All extract preparations at multiple concentrations were significantly effective as evidenced by MTT assay when compared to the control group. The IC50 level for Triphala extract was 77.63 ± 4.3 µg/ml. Based on the results, Triphala and its components have cytotoxic activity on the HepG2 cancer cell line and they can reduce the survival rate significantly.

Taccachatrones A-G, Highly Oxidized Steroids from the Rhizomes of Tacca chantrierii and Their Cytotoxicity Assessment.

Seven highly oxidized steroids, taccachatrones A-G (1-7), together with four known taccalonolides (8-11), were characterized from the rhizomes of Tacca chantrieri. The structures of 1-7 were established on the basis of spectroscopic data analysis, while the absolute configurations were determined by single-crystal X-ray diffraction. Compounds 1-4 may be derived from taccalonolide derivatives by the degradation of three carbon atoms. Compounds 7, 8, 10, and 11 exhibited cytotoxicity to human cancer cell lines, indicating that the presence of a lactone moiety, as well as a double bond between C-22 and C-23, might play key roles in mediating their cytotoxicity.

Assessment of Chemopreventive Potential of the Plant Extracts against Liver Cancer Using HepG2 Cell Line.

The edible parts of the plants Camellia sinensis, Vitis vinifera and Withania somnifera were extensively used in ancient practices such as Ayurveda, owing to their potent biomedical significance. They are very rich in secondary metabolites such as polyphenols, which are very good antioxidants and exhibit anti-carcinogenic properties. This study aims to evaluate the anti-cancerous properties of these plant crude extracts on human liver cancer HepG2 cells. The leaves of Camellia sinensis, Withania somnifera and the seeds of Vitis vinifera were collected and methanolic extracts were prepared. Then, these extracts were subjected to DPPH, α- amylase assays to determine the antioxidant properties. A MTT assay was performed to investigate the viability of the extracts of HepG2 cells, and the mode of cell death was detected by Ao/EtBr staining and flow cytometry with PI Annexin- V FITC dual staining. Then, the protein expression of BAX and BCl2 was studied using fluorescent dye to determine the regulation of the BAX and BCl2 genes. We observed that all the three extracts showed the presence of bioactive compounds such as polyphenols or phytochemicals. The W. somnifera bioactive compounds were found to have the highest anti-proliferative activity on human liver cancer cells.

New cytotoxic dichapetalins in the leaves of Phyllanthus acidus: Identification, quantitative analysis, and preliminary toxicity assessment.

The young leaves of Phyllanthus acidus (Euphorbiaceae) are commonly used as edible vegetables in Indonesia, Thailand, and India, and their water infusions as dieting aids for people trying to remain slim. However, it is regarded as a poisonous plant in Malaya, and current researches are insufficient to provide a conclusion on its toxicity and safety under large doses. In this study, we firstly found that the refined nonpolar extracts of P. acidus leaves showed significant cytotoxic effect against BEAS-2B and L02 normal cell lines with IC50 values of 2.15 and 1.64 mg/mL, respectively. Further bioactivity-guided isolation produced four new rare dichapetalins (pacidusins A-D) from the most active fraction. Their structures including absolute configurations were elucidated by extensive spectroscopic data and X-ray diffraction analysis. All the isolated dichapetalins exhibited moderate cytotoxicity against, BEAS-2B and L02 normal cell lines with IC50 values ranging from 12.44 to 22.55 µM, as well as five human cancer cell lines with IC50 values ranging from 3.38 to 22.38 µM. Furthermore, the content of the main dichapetalins in the leaves were determined by analytical HPLC, which showed that the leaves contained a very high amount of the four isolated dichapetalins with a total yield of 0.488 mg/g of dry plant material. These toxic dichapetalins may lead to adverse health effects in higher doses. Our findings indicate that the dichapetalin containing leaves may not be suitable for consumption in large quantities as food, but demonstrate their potency as anti-cancer agents for new drug discovery.

Assessment of Betulinic Acid Cytotoxicity and Mitochondrial Metabolism Impairment in a Human Melanoma Cell Line.

Melanoma represents one of the most aggressive and drug resistant skin cancers with poor prognosis in its advanced stages. Despite the increasing number of targeted therapies, novel approaches are needed to counteract both therapeutic resistance and the side effects of classic therapy. Betulinic acid (BA) is a bioactive phytocompound that has been reported to induce apoptosis in several types of cancers including melanomas; however, its effects on mitochondrial bioenergetics are less investigated. The present study performed in A375 human melanoma cells was aimed to characterize the effects of BA on mitochondrial bioenergetics and cellular behavior. BA demonstrated a dose-dependent inhibitory effect in both mitochondrial respiration and glycolysis in A375 melanoma cells and at sub-toxic concentrations (10 µM) induced mitochondrial dysfunction by eliciting a decrease in the mitochondrial membrane potential and changes in mitochondria morphology and localization. In addition, BA triggered a dose-dependent cytotoxic effect characterized by apoptotic features: morphological alterations (nuclear fragmentation, apoptotic bodies) and the upregulation of pro-apoptotic markers mRNA expression (Bax, Bad and Bak). BA represents a viable therapeutic option via a complex modulatory effect on mitochondrial metabolism that might be useful in advanced melanoma or as reliable strategy to counteract resistance to standard therapy.

Bioactive benzoquinones content variability in red-berry and white-berry varieties of Ardisia crenata Sims. and assessment of cytotoxic activity.

Ardisia crenata Sims (Myrsinaceae) occurs in two varieties differing in the fruit color, the red berries being common while the white ones are rare. The roots of red-berried A. crenata are a valued TCM product which contains bioactive benzoquinones such as embelin and rapanone. In this study we compared their profiles in different organs of the plant to provide an insight in the pattern of their accumulation within the two varieties. Moreover, cytotoxic activity against human melanoma and prostate cancer cells was evaluated. Quantitative HPLC revealed that the white-berried variety differs profoundly in the content of rapanone, with its total level of 606.5 mg/100 g d.w., as compared to 16.2 mg/100 g d.w. in A. crenata 'red'. Embelin was less distributed and found in minor amounts in both varieties. This is the first report on rapanone content in various parts of Ardisia crenata and on benzoquinones in the white-berried variety.

Assessment of the Biological Activity and Phenolic Composition of Ethanol Extracts of Pomegranate (Punica granatum L.) Peels.

Pomegranate (Punica granatum L.) is a rich source of constituents with confirmed strong biological activities. However, pomegranate peel, which encompasses approximately 30-40% of its weight, is treated as a biological waste. The aim of this paper was to evaluate the potential of pomegranate peel extracts and to propose its functional properties that can be used for development of functional products. Eight ethanol extracts of pomegranate peels (PPEs) were characterized by use of direct infusion quadrupole-time of flight (Q-TOF), and afterwards tested on their antioxidant, antibacterial and antiproliferative activities. Mass spectrometry analysis revealed that the most prevalent compounds in pomegranate peels were punicalagin, granatin and their derivatives. Analysed extracts had high total phenolic contents that ranged from 5766.44 to 10599.43 mg GAE/100 g, and strong antioxidant activity (7551.31-7875.42 and 100.25-176.60 µmol TE/100 g for DPPH and FRAP assays, respectively). The results of biological activity assays showed that all PPEs possessed antibacterial activity, and that S. aureus was the most sensitive specie with minimum inhibitory concentration and minimum bactericidal concentrations ranging from 0.8 to 6.4 mg/mL. Additionally, the analysis of antiproliferative activity revealed high potency of PPEs, as the IC50 values ranged from 0.132 mg/mL to 0.396 mg/mL. Multivariate analysis pointed out the most discriminative metabolites for antioxidant or antiproliferative activity. Overall, the pomegranate peel confirmed to be a highly valuable source of bioactive compounds that could be used to improve the food functional characteristics.

Essential Oil from Melaleuca leucadendra: Antimicrobial, Antikinetoplastid, Antiproliferative and Cytotoxic Assessment.

Essential oils (EOs) are known for their use in cosmetics, food industries, and traditional medicine. This study presents the chemical composition and therapeutic properties against kinetoplastid and eukaryotic cells of the EO from Melaleucaleucadendra (L.) L. (Myrtaceae). Forty-five compounds were identified in the oil by GC-MS, containing a major component the 1,8-cineole (61%). The EO inhibits the growth of Leishmania amazonensis and Trypanosoma brucei at IC50 values <10 µg/mL. However, 1,8 cineole was not the main compound responsible for the activity. Against malignant (22Rv1, MCF-7, EFO-21, including resistant sublines MCF-7/Rap and MCF-7/4OHTAMO) and non-malignant (MCF-10A, J774A.1 and peritoneal macrophage) cells, IC50 values from 55 to 98 µg/mL and from 94 to 144 µg/mL were obtained, respectively. However, no activity was observed on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, Candida parapsilosis, Microsporum canis, or Trypanosoma cruzi. The EO was able to control the lesion size and parasite burden in the model of cutaneous leishmaniasis in BALB/c mice caused by L. amazonensis compared to untreated animals (p < 0.05) and similar with those treated with Glucantime® (p > 0.05). This work constitutes the first evidence of antiproliferative potentialities of EO from M. leucadendra growing in Cuba and could promote further preclinical investigations to confirm the medical value of this plant, in particular for leishmaniasis treatment.

DEP-Dots for 3D cell culture: low-cost, high-repeatability, effective 3D cell culture in multiple gel systems.

It is known that cells grown in 3D are more tolerant to drug treatment than those grown in dispersion, but the mechanism for this is still not clear; cells grown in 3D have opportunities to develop inter-cell communication, but are also closely packed which may impede diffusion. In this study we examine methods for dielectrophoresis-based cell aggregation of both suspension and adherent cell lines, and compare the effect of various drugs on cells grown in 3D and 2D. Comparing viability of pharmacological interventions on 3D cell clusters against both suspension cells and adherent cells grown in monolayer, as well as against a unicellular organism with no propensity for intracellular communication, we suggest that 3D aggregates of adherent cells, compared to suspension cells, show a substantially different drug response to cells grown in monolayer, which increases as the IC50 is approached. Further, a mathematical model of the system for each agent demonstrates that changes to drug response are due to inherent changes in the system of adherent cells from the 2D to 3D state. Finally, differences in the electrophysiological membrane properties of the adherent cell type suggest this parameter plays an important role in the differences found in the 3D drug response.

Assessment of In Vitro Anti-melanoma Potential of Ephedranthus pisocarpus R.E.Fr.

BACKGROUND/AIM: Despite being a rare disease, melanoma is considered the most dangerous skin cancer due to its highly invasive and aggressive nature, and still requires for more effective treatments. The aim of this study was to evaluate the in vitro anti-melanoma potential of Ephedranthus pisocarpus R.E.Fr. (Annonaceae), a popular Brazilian plant with medicinal properties. MATERIALS AND METHODS: Initially, the ethanolic extract (EtOH) was obtained from E. pisocarpus leaves and later partitioned using increasing polarity solvents. The anti-melanoma potential of E. pisocarpus was assessed by spectrophotometry and its cytotoxicity determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and confocal microscopy. RESULTS: We demonstrated that the EtOH extract and fractions from E. pisocarpus had a moderate photoprotective action (FPS 3.0-5.0) against UVA radiation. Interestingly, the dichloromethane fraction presented higher anti-melanoma activity against B16-F10 (IC50=46.8 µg/ml) and SK-MEL-28 cells (IC50=40.1 µg/ml) and lesser toxicity on normal cells. Additionally, our study reported that spathulenol, one of the major constituents from E. pisocarpus, acts through an apoptosis-dependent mechanism in SK-MEL-28 cells. CONCLUSION: The present study demonstrated, for the first time, the in vitro anti-melanoma potential of E. pisocarpus against melanoma cells.

Analysis of Chemical Composition and Assessment of Antioxidant, Cytotoxic and Synergistic Antibacterial Activities of Essential Oils from Different Plant Parts of Piper boehmeriifolium.

The essential oils (EOs) from leaves, stems, and whole plant of Piper boehmeriifolium were analyzed using GC/FID and GC/MS. The main constituents of P. boehmeriifolium EOs were ß-caryophyllene, caryophyllene oxide, ß-elemene, spathulenol, germacrene D, ß-selinene, and neointermedeol. The antioxidant potential of the EOs were determined using DPPH• , ABTS•+ and FRAP assays. In ABTS•+ assay, the leaf oil exhibited a remarkable activity with an IC50 value of 7.36 µg/mL almost similar to BHT (4.06 µg/mL). Furthermore, the antibacterial activity of the oils as well as their synergistic potential with conventional antibiotics were evaluated using microdilution and Checkerboard assays. The results revealed that the oils from different parts of P. boehmeriifolium inhibited the growth of all tested bacteria and the minimum inhibitory concentrations were determined to be 0.078 - 1.250 mg/mL. In combination with chloramphenicol or streptomycin, the oils showed significant synergistic antibacterial effects in most cases. Besides, the results of MTT assay indicated that the oil of the whole plant exhibited significant cytotoxic activities on human hepatocellular carcinoma cells (HepG2) and human breast cancer cells (MCF-7). In summary, the P. boehmeriifolium oils could be regarded as a prospective source for pharmacologically active compounds.

Synthesis and Evaluation of Ga-68-Labeled Rhein for Early Assessment of Treatment-Induced Tumor Necrosis.

PURPOSE: This study aimed to synthesize a necrosis-avid agent using rhein as a precursor and labeled with gallium-68 (Ga-68) for positron emission tomography/computed tomography (PET/CT) imaging, to evaluate response to anticancer treatment in a mouse model. PROCEDURES: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated rhein was radiolabeled with Ga-68 to formulate [68Ga]DOTA-rhein. The in vitro stability of [68Ga]DOTA-rhein was assessed by radio-HPLC. Necrosis avidity was evaluated in a mouse model of muscle necrosis by microPET/CT imaging, biodistribution study, histochemical staining, and autoradiography studies. Murine tumor models with the subcutaneous implantation of S180 cell lines were generated for the evaluation of therapeutic effect. Tumor necrosis was induced by the treatment of combretastatin A4 disodium phosphate (CA4P), and microPET/CT imaging was performed at 1 h post tracer injection. DNA binding studies were conducted to explore the necrosis avidity mechanism of the tracer. RESULTS: [68Ga]DOTA-rhein exhibited a satisfactory yield, a radiochemical purity over 97 %, and a good serum stability. The uptakes of [68Ga]DOTA-rhein in necrotic muscles and tumors were significantly higher than those in normal muscles and tumors (P < 0.05). The results of autoradiography and histochemical staining were consistent with the selective uptake of the radiotracer in necrotic regions. MicroPET/CT images showed a high uptake of the tracer in necrotic muscles and necrotic tumors. DNA binding studies suggested that necrosis avidity correlated with DNA binding to a certain extent. CONCLUSIONS: Our results demonstrated that [68Ga]DOTA-rhein showed a prominent necrosis avidity and could be a useful probe for early assessment of response to anticancer therapy by PET/CT imaging.

Assessment of the cytotoxic effects of aporphine prototypes on head and neck cancer cells.

Purpose Among alkaloids, abundant secondary metabolites in plants, aporphines constitute a class of compounds with interesting biological activities, including anticancer effects. The present study evaluated the anticancer activities of 14 substances, including four aporphine derivatives acquired through the biomonitoring of (±)-apomorphine hydrochloride total synthesis from 2-phenethylamine and 3,4-dimethoxybenzaldehyde against head and neck squamous cell carcinoma (HNSCC). Methods The cytotoxic effects of compounds against a panel of HNSCC cell lines were determined by PrestoBlue cell viability assay, while the genotoxicity of substances was evaluated by micronucleus test. Cell death was detected by flow cytometry (Annexin V/7AAD) and western blot analysis was used to detect the presence of cleaved Caspase-3 molecules. Results The aporphine and isoquinoline derivatives APO, C1, and A5 significantly reduced HNSCC cell viability and promoted DNA damages in these cells. Further, by activating the Caspase-3 pathway, these substances were able to induce apoptosis. Conclusion Our results revealed that APO, C1, and A5 exhibit cytotoxic effects in HNSCC cells. The mechanisms of action appear to be partly via the generation of DNA damages and apoptosis induction through Caspase-3 pathway activation. This study provides preclinical data that suggest a potential therapeutic role for APO, C1, and A5 against head and neck cancer cells.

The Market Reacts Quickly: Changes in Paclitaxel Vascular Device Purchasing Within the Ascension Healthcare System.

BACKGROUND: A meta-analysis of trials in endovascular therapy suggested an increased mortality associated with treatment exposure to paclitaxel. Multiple publications and corrections of prior data were performed, and the United States Food and Drug Administration has issued multiple advisories regarding paclitaxel use. We analyzed how this controversy impacted device purchasing and related utilization patterns in the period immediately following publication of the meta-analysis. METHODS AND RESULTS: Ascension Healthcare System purchase data over a 14-month period were synthesized across centers for both paclitaxel and non-paclitaxel devices. A fixed-effects regression model and a binary regression model with facility-level controls were used to compare purchasing patterns before and after the meta-analysis. Purchase volumes of each paclitaxel device fell. Pooled purchase volumes of all paclitaxel devices decreased from a 14-month peak of 631 devices in October 2018 to a 14-month nadir of 359 devices in February 2019. An F-test comparing the pooled-month specific fixed effects for the months before vs after the publication of the meta-analysis has an F-statistic of 11.64, suggesting that average purchasing levels in the two periods are statistically different (P<.001). Utilization of non-paclitaxel devices did not decline. CONCLUSIONS: Purchase volumes of paclitaxel devices decreased immediately during the months following publication of the related meta-analysis. Total Ascension-wide paclitaxel device purchase volume in February 2019 demonstrated a 43.1% reduction from peak monthly purchase volume during the assessed period and a 32.5% reduction compared with November 2019, the last month preceding publication of the meta-analysis.

An integrated approach for the valorization of mango seed kernel: Efficient extraction solvent selection, phytochemical profiling and antiproliferative activity assessment.

A novel valorization strategy is proposed in this work for the sustainable utilization of a major mango processing waste (i.e. mango seed kernel, MSK), integrating green pressurized-liquid extraction (PLE), bioactive assays and comprehensive HRMS-based phytochemical characterization to obtain bioactive-rich fractions with high antioxidant capacity and antiproliferative activity against human colon cancer cells. Thus, a two steps PLE procedure was proposed to recover first the non-polar fraction (fatty acids and lipids) and second the polar fraction (polyphenols). Efficient selection of the most suitable solvent for the second PLE step (ethanol/ethyl acetate mixture) was based on the Hansen solubility parameters (HSP) approach. A comprehensive GC- and LC-Q-TOF-MS/MS profiling analysis allowed the complete characterization of the lipidic and phenolic fractions obtained under optimal condition (100% EtOH at 150 °C), demonstrating the abundance of oleic and stearic acids, as well as bioactive xanthones, phenolic acids, flavonoids, gallate derivatives and gallotannins. The obtained MSK-extract exhibited higher antiproliferative activity against human colon adenocarcinoma cell line HT-29 compared to traditional extraction procedures described in literature for MSK utilization (e.g. Soxhlet), demonstrating the great potential of the proposed valorization strategy as a valuable opportunity for mango processing industry to deliver a value-added product to the market with health promoting properties.

The NCI library of traditional Chinese medicinal plant extracts - Preliminary assessment of the NCI-60 activity and chemical profiling of selected species.

Botanical-based natural products are an important resource for medicinal drug discovery and continue to provide diverse pharmacophores with therapeutic potential against cancer and other human diseases. A prototype Traditional Chinese Medicine (TCM) plant extract library has been established at the US National Cancer Institute, which contains both the organic and aqueous extracts of 132 authenticated medicinal plant species that collectively represent the potential therapeutic contents of most commonly used TCM herbal prescriptions. This library is publicly available in 96- and 384- well plates for high throughput screening across a broad array of biological targets, as well as in larger quantities for isolation of active chemical ingredients. Herein, we present the methodology used to generate the library and the preliminary assessment of the anti-proliferative activity of this crude extract library in NCI-60 human cancer cell lines screen. Particularly, we report the chemical profiling and metabolome comparison analysis of four commonly used TCM plants, namely Brucea javanica, Dioscorea nipponica, Cynanchum atratum, and Salvia miltiorrhiza. Bioassay-guided isolation resulted in the identification of the active compounds, and different extraction methods were compared for their abilities to extract cytotoxic compounds and to concentrate biologically active natural products.