Magnetic Nanoparticles for the Delivery of Dapagliflozin to Hypoxic Tumors: Physicochemical Characterization and Cell Studies

In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors. The magnetic nanoparticles consisted of a magnetic iron oxide core and a poly(methacrylic acid)-graft-poly(ethyleneglycol methacrylate) (PMAA-g-PEGMA) polymeric shell. The drug (dapagliflozin) molecules were conjugated on the surface of these nanoparticles via in vivo hydrolysable ester bonds. The nanoparticles had an average size of ~ 70 nm and exhibited a DAPA loading capacity 10.75% (w/w) for a theoretical loading 21.68% (w/w). The magnetic responsiveness of the nanoparticles was confirmed with magnetophoresis experiments. The dapagliflozin-loaded magnetic nanoparticles exhibited excellent colloidal stability in aqueous and biological media. Minimal (less than 15% in 24 h) drug release from the nanoparticles occurred in physiological pH 7.4; however, drug release was significantly accelerated in pH 5.5. Drug release was also accelerated (triggered) under the influence of an alternating magnetic field. The DAPA-loaded nanoparticles exhibited higher in vitro anticancer activity (cytotoxicity) against A549 human lung cancer cells than free DAPA. The application of an external magnetic field gradient increased the uptake of nanoparticles by cells, leading to increased cytotoxicity. The results justify further in vivo studies of the suitability of DAPA-loaded magnetic nanoparticles for the treatment of hypoxic tumors.     

Liposomal formulation for co-delivery of paclitaxel and lapatinib,preparation, characterization and optimization

Paclitaxel (PTX) is one of the most promising natural anticancer agents with a wide therapeutic range which is limited by its hydrophobic nature, low therapeutic index and more importantly, the emergence of multidrug resistance (MDR). Lapatinib (LPT) is a dual tyrosine kinase inhibitor with a significant potential to inhibit p-glycoproteins which form one of the main groups of proteins responsible for efflux pump mediated MDR. To overcome the PTX related MDR, a novel liposomal formulation was optimized for co-delivery of PTX and LPT by applying the D-optimal response surface methodology. The encapsulation efficiency (EE%) of the optimized formulation for LPT and PTX was 52?±?3% and 68?±?5, respectively. The optimized formulation showed a narrow size distribution with the average of 235?±?12?nm. The transmission electron microscopy image showed that liposomes were round in shape and discrete. The release profile exhibited 93% and 71% drug release for PTX and LPT after 40?h in the sink condition. The differential scanning calorimetry analysis indicated the conversion of both drugs from crystalline state to molecular state in the optimized lyophilized formulation. The cytotoxicity of the prepared formulation was studied against 4T1 murine mammary cells. The liposomal formulation showed better cytotoxicity in comparison to the binary mixture of free drugs.     

Self-Assembling Raloxifene Loaded Mixed Micelles: Formulation Optimization, <Emphasis Type="Italic">In Vitro</Emphasis> Cytotoxicity and <Emphasis Type="Italic">In Vivo</Emphasis> Pharmacokinetics

Raloxifene (RLX) has been strongly recommended for postmenopausal women at high risk of invasive breast cancer and for prevention of osteoporosis. However, low aqueous solubility and reduced bioavailability hinder its clinical application. The objective of this study was to explore the potential of RLX loaded mixed micelles (RLX-MM) using Pluronic F68 and Gelucire 44/14 for enhanced bioavailability and improved anticancer activity on human breast cancer cell line (MCF-7). RLX-MM were prepared by solvent evaporation method and optimized using 3² factorial design. The average size, entrapment efficiency and zeta potential of the optimized formulation were found to be 190?±?3.3 nm, 79?±?1.3%, 13?±?0.8 mV, respectively. In vitro study demonstrated 74.68% drug release from RLX-MM in comparison to 42.49% drug release from RLX dispersion. According to the in vitro cytotoxicity assay, GI₅₀ values on MCF-7 breast cancer cell line for RLX-MM and free RLX were found to be 22.5 and 94.71 μg/mL, respectively. Significant improvement (P?<?0.05) in the anticancer activity on MCF-7 cell line was observed in RLX-MM over RLX pure drug. Additionally, oral bioavailability of RLX-MM was improved by 1.5-fold over free RLX when administered in female Wistar rats. Incorporation of RLX in the hydrophobic core and improved solubility of the drug due to hydrophilic shell attributed to the enhanced cytotoxicity and bioavailability of RLX-MM. This research establishes the potential of RLX loaded mixed micelles of Pluronic F68 and Gelucire 44/14 for improved bioavailability and anticancer activity on MCF-7 cell line.     

Synthesis and biological evaluation of paclitaxel and vorinostat co-prodrugs for overcoming drug resistance in cancer therapy in vitro

Paclitaxel (PTX) is the first-line treatment drug for breast cancer. However, drug resistance after a course of treatment and low selectivity restricted its clinical utility sometimes. In this study, we successfully bound PTX and vorinostat (SAHA) to form co-prodrugs based on the synergistic anticancer effects. The PTX-SAHA co-prodrugs were conjugated by glycine (1a) and succinic acid (1b) respectively and the former has shown better activity in cytotoxicity, cell cycle arrest and western-blot experiments. Therefore, 1a was further prepared to nanomicelles with mPEG₂₀₀₀-PLA₁₇₅₀ as the carrier by using thin film method. PTX-SAHA co-prodrug nanomicelles were spherical with a particle size of 20–100?nm. In vitro drug release test showed 1a nanomicelles had sustained release effect, which could reduce the resistance of PTX. In vitro cytotoxicity was evaluated by SRB assay in HCT-116 cells, MCF-7 cells and drug-resistant MCF-7/ADR cells. The results showed 1a nanomicelles had comparable or even better cytotoxicity than PTX especially in the MCF-7/ADR cells. All the results suggested that PTX-SAHA co-prodrug nanomicelles were promising treatment for PTX resistance cancer.     

Antineoplastic drug‐loaded polymer‐modified magnetite nanoparticles: Comparative analysis of EPR‐mediated drug delivery

This study aimed to design and evaluate enhanced permeation and retention (EPR)‐mediated anticancer effect of polymer‐modified and drug‐loaded magnetite nanocomposites. The preformulated bare (10 nm), chitosan‐superparamagnetic iron oxide (SPIO; 69 nm), heparin‐SPIO (42 nm), and (3‐aminopropyl)triethoxysilane‐polyethylene glycol‐SPIO (17 nm) nanocomposites were utilized to evaluate the EPR‐mediated localized cancer targeting and retention of doxorubicin (DOX) and paclitaxel (PTX) in human ovarian cancer cell lines, A2780 and OVCAR‐3 in vitro and in the tumor‐baring Balb/c mice in vivo. Fluorescence microscopy showed that DOX‐ and PTX‐loaded SPIO nanoparticles caused long‐term accumulation and cytoplasmic retention in A2780 and OVCAR‐3 cells, as compared to free drugs in vitro. In vivo antiproliferative effect of present formulations on immunodeficient female Balb/c mice showed a tremendous amount of ovarian tumor shrinkage within 6 weeks. The present nanocomposite systems of targeted drug delivery proved to be efficient drug carrier with sustained drug release and long‐term retention with enhanced cytotoxic properties in vitro and in vivo.     

Controllable release of self-assembled reduction-sensitive paclitaxel dimer prodrug and tetrandrine nanoparticles promotes synergistic therapy against multidrug-resistant cancer

BackgroundMultidrug resistance (MDR) is the main reason for chemotherapy failure. Nanocarriers combined delivery of anti-cancer drugs and MDR inhibitors is an effective strategy to avoid MDR and improve the anti-cancer activity of drugs.MethodsTwo paclitaxel (PTX) molecules are linked by disulfide bonds into PTX₂. Then, the PTX₂ and tetrandrine (TET) are coated together by mPEG-PLGA self-assembled NPs for combinational treatment. Microstructure, physiological stability, and cytotoxicity are characterized for the co-loaded NPs.ResultsThe NPs exhibit excellent suitability and blood safety for intravenous injection, specifically responsive to pH 6–7, and promptly initiate chemical degradation. Ex vivo fluorescence microscopy image studies indicate that co-loaded NPs increase drug penetration into cancer cells compared with free drugs. MTT assay demonstrates that co-loaded NPs have higher cytotoxicity against HeLa and the flow cytometric analysis shows that co-loaded NPs trigger more apoptosis than the free drugs. Reactive oxygen species (ROS) assay indicates that the drug-loaded NPs generated higher levels of ROS to accelerate apoptosis in HeLa cells.ConclusionsTET can get desirable effects of inhibiting the MDR in advance by binding with the active site on P-gp, then the disulfide bond of PTX₂ is broken by glutathione (GSH) in cancer cells and decomposed into PTX to inhibit cancer cell proliferation.General significanceOur studies indicate that the co-loaded NPs can potentially overcome the MDR of conventional chemotherapeutic agents.     

Evaluating cytotoxic effect of nanoliposomes encapsulated with umbelliprenin on 4T1 cell line

Cytotoxicity of umbelliprenin has been found in various cancer cell lines such as, prostate, breast, CLL, and skin. Encapsulating chemotherapeutic agents with nanoliposomes have been resulted in improved cytotoxicity effects than their free forms. However, whether nanoliposomal form of umbelliprenin could have higher cytotoxic effect than free umbelliprenin is not clarified yet. After synthesizing umbelliprenin, different concentrations (3, 6, 12, 25, 50, 100, 200 μg/ml) applied on the mouse mammary carcinoma cell line (4T1) for 24, 48, and 72 h at 37°C. Afterwards, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to analyze cytotoxicity. MTT assay results showed that IC₅₀ of umbelliprenin in dimethyl sulfoxide (DMSO) (30.92, 30.64, and 62.23 for 24, 48, 72 h incubation, respectively) decreased (5.8, 5.0, 3.5 for 24, 48, 72 h incubation, respectively) when encapsulated with nanoliposomes. Nanoliposomal umbelliprenin cytotoxicity affected cell viability in concentration and time-dependent manner. Our study recommended nanoliposomal umbelliprenin as the most effective chemotherapeutic agent against the mouse mammary carcinoma cell line viability. Future in vivo studies and clinical trials are needed.     

In Vitro Anticancer Activity of Staphyloxanthin Pigment Extracted from <Emphasis Type="Italic">Staphylococcus gallinarum</Emphasis> KX912244, a Gut Microbe of <Emphasis Type="Italic">Bombyx mori</Emphasis>

The present study reports the in vitro biological nature of the pigment produced by Staphylococcus gallinarum KX912244, isolated as the gut microflora bacterium of the insect Bombyx mori. The purified pigment was characterized as Staphyloxanthin based on bio-physical characterization techniques like Fourier transform infrared spectroscopy, high performance liquid chromatography, Proton nuclear magnetic resonance spectroscopy (¹H NMR), Liquid chromatography-Mass spectroscopy and Gas chromatography-Mass spectroscopy. The Staphyloxanthin pigment presented considerable biological properties including in vitro antimicrobial activity against pathogens Staphylococcus aureus, Escherichia coli and Candida albicans; in vitro antioxidant activity by % DPPH free radical scavenging activity showing IC₅₀ value of 54.22 µg/mL; DNA damage protection activity against reactive oxygen species and anticancer activity evaluated by cytotoxicity assay against 4 different cancer cell lines like the Dalton’s lymphoma ascites with IC₅₀ value 6.20?±?0.02 µg/mL, Ehrlich ascites carcinoma having IC₅₀ value 6.48?±?0.15 µg/mL, Adenocarcinomic human alveolar basal epithelial cells (A549 Lung carcinoma) bearing IC₅₀ value 7.23?±?0.11 µg/mL and Mus mucus skin melanoma (B16F10) showing IC₅₀ value 6.58?±?0.38 µg/mL and less cytotoxicity towards non-cancerous human fibroblast cell lines (NIH3T3) with IC₅₀ value of 52.24 µg/mL. The present study results suggest that Staphyloxanthin acts as a potential therapeutic agent especially due to its anticancer property.     

Ifosfamide-loaded lipid-core-nanocapsules to increase the anticancer efficacy in MG63 osteosarcoma cells

In this study, we mainly aimed at developing the Ifosfamide-loaded-lipid-core nanocapsules (IFS-LNC) to increase the therapeutic efficacy in osteosarcoma. The nanoparticle was prepared and evaluated in terms of physical, chemical and biological parameters. The lipid-core-nanocapsules were nanosized with narrow particle size distribution and exhibited a high loading capacity. The LNC displayed a sustained release profile of the drug suggesting its potential application in biomedical field and prolonged anticancer therapy. The LNC showed an endocytosis-mediated cellular uptake in MG63 cancer cells which may lead to an accelerated disruption of the acidic endolysosomal vesicles with release of IFS into the cytoplasm. Specifically, IFS-LNC exhibited a significantly higher cytotoxicity than free IFS used at the same concentration. The indiscriminate ability of the drug-loaded formulation increased the apoptosis of cancer cells by increasing the expression levels of caspase-3 and caspase-9 in MG63 cells. Overall, nanoparticulate formulations of Ifosfamide enhanced the therapeutic efficacy in osteosarcoma.     

Antibacterial,anti-biofilm and anticancer potentials of green synthesized silver nanoparticles using benzoin gum (<Emphasis Type="Italic">Styrax benzoin</Emphasis>) extract

This study described a simple and green approach for the synthesis of silver nanoparticles (AgNPs) employing benzoin gum water extract as a reducing and capping agent and their applications. The AgNPs were characterized by ultraviolet–visible spectrophotometer, X-ray diffraction pattern, field emission transmission electron microscopy, dynamic light scattering, zeta potential and fourier transform infrared spectroscopy. The AgNPs showed promising antimicrobial activity against various pathogens (Gram-negative, Gram-positive and fungus) and possessed high free radical scavenging activity (104.5 ± 7.21 % at 1 mg/ml). In addition, the AgNPs exhibited strong cytotoxicity towards human cervical cancer and human lung cancer cells as compared to the normal mouse macrophage cells. Moreover, the AgNPs possessed anti-biofilm activity against Escherichia coli, and compatibility to human keratinocyte HaCaT cells, which suggests the use of dressing with the AgNPs in chronic wound treatment. Therefore, AgNPs synthesized by benzoin gum extract are comparatively green and may have broad spectrum potential application in biomedicine.     

Antitumor Peptides from <Emphasis Type="Italic">Streptomyces</Emphasis> sp. SSA 13, Isolated from Arabian Sea

As part of the endeavor for search of effective bioactive compounds, an untapped Arabian Sea environment is selected as a sampling source for the isolation of chemically-talented actinomycete strains. We have isolated an actinomycete strain from the sea sediments belonging to the genus Streptomyces (Accession No. KJ020688) with having potent cytotoxicity (84 %) against brine shrimps nauplii. Isolated strain also showed substantial antibacterial activity against Bacilus subtilis, Escherichia coli and Acinetobacter test strains. Fractions with significant antitumor activity obtained from the extract of 20 l fermentation broth were structurally elucidated and revealed with the production of compounds named as iturin A₆ and actinomycin-D. The cyclic lipopeptide iturin A₆ display outstanding novel antitumor activities against three tumor cell lines viz. HeLa, MCF-7, Hep G2 with IC₅₀ values of 1.73 ± 0.9, 6.44 ± 0.6 and 8.9 ± 1.09 μg/ml respectively. This peptide is found to be ineffective against RD tumor cells. The second polypeptide actinomycin-D is found to be active against the entire panel of tumor cell lines used. It exhibited stronger activities with IC₅₀-values of <0.9 μg/ml against HeLa and MCF-7, while 11.72 ± 0.9 and 1.19 ± 0.8 against Hep G2 and RD cells respectively. Results from the culture optimization experiments of this strain showed greater yield of secondary metabolites while culturing in glucose–yeast extract–malt extract (M2) medium under culture conditions set as follows, shaking at 95 rpm, pH 7.8, incubation temperature 28 °C, for 168 h. As such this is the first report for the isolation of any iturin family member from actinomycetes group with having antitumor activity.     

Preparation of an injectable doxorubicin surface modified cellulose nanofiber gel and evaluation of its anti‐tumor and anti‐metastasis activity in melanoma

Cellulose nanofibers (Cel‐NFs) gel can be considered as a useful drug carrier because of its biocompatibility, high specific surface area, and high loading capacity of drugs. Injectable Cel‐NFs gel could deliver doxorubicin (DOX) for localized chemotherapy of melanoma and suppress melanoma cells migration because of the physical barrier property of Cel‐NFs. We prepared DOX surface modified Cel‐NFs (DOX‐Cel‐NFs) gel by the electrostatic attachment of DOX molecules on the surface of Cel‐NFs. The increase in the zeta potential of nanofibers and the changes in the FTIR spectra of DOX‐Cel‐NFs compared to Cel‐NFs proved this attachment. DOX‐Cel‐NFs showed nano‐fibrous structure with an average diameter of 22.32 ± 10.66 nm after analyzing using field emission scanning electron microscopy. The suitable injectability of DOX‐Cel‐NFs gel verified its promising application for the localized chemotherapy. DOX‐Cel‐NFs gel exhibited a sustained drug release manner. The cytotoxicity results showed that DOX‐Cel‐NFs were more cytotoxic against melanoma cancer cells than the free DOX during 48 h incubation period. Moreover, DOX‐Cel‐NFs gel can suppress the melanoma cancer cells migration efficiently. Thus our results emphasize the potential of DOX‐Cel‐NFs gel as a chemotherapeutic agent for local delivery of DOX in order to treat melanoma and prevent its metastasis. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:537–545, 2018     

Design,synthesis, and cytotoxic activity of novel 7-substituted camptothecin derivatives incorporating piperazinyl-sulfonylamidine moieties

In our continuing search for camptothecin (CPT)-derived antitumor drugs, novel 7-substituted CPT derivatives incorporating piperazinyl-sulfonylamidine moieties were designed, synthesized and evaluated for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB, and KB-VIN). All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, and were more potent than irinotecan. Remarkably, most of the compounds exhibited comparable cytotoxicity against the multidrug-resistant (MDR) KB-VIN and parental KB tumor cell lines, while irinotecan lost activity completely against KB-VIN. Especially, compounds 13r and 13p (IC₅₀ 0.38 and 0.85 μM, respectively) displayed the greatest cytotoxicity against the MDR KB-VIN cell line and merit further development into preclinical and clinical drug candidates for treating cancer, including MDR phenotype.     

Development of multifunctional hyaluronan-coated nanoparticles for imaging and drug delivery to cancer cells

Currently, there is high interest in developing multifunctional theranostic platforms for cancer monitoring and chemotherapy. Herein, we report hyaluronan (HA)-coated superparamagnetic iron oxide nanoparticles (HA-SPION) as a promising system for targeted imaging and drug delivery. When incubated with cancer cells, HA-SPIONs were rapidly taken up and the internalization of HA-SPION by cancer cells was much higher than the NPs without HA coating. The high magnetic relaxivity of HA-SPION coupled with enhanced uptake enabled magnetic resonance imaging of cancer cells. Furthermore, doxorubicin (DOX) was attached onto the nanoparticles through an acid responsive linker. While HA-SPION was not toxic to cells, DOX-HA-SPION was much more potent than free DOX to kill not only drug-sensitive but also multi-drug-resistant cancer cells. This was attributed to differential uptake mechanisms and cellular distributions of free DOX and DOX-HA-SPION in cancer cells.     

Optimization of <Emphasis Type="Italic">Curcuma</Emphasis> Oil/Quinine-Loaded Nanocapsules for Malaria Treatment

Quinine, a treatment used in chloroquine-resistant falciparum malaria, was loaded into poly(?-caprolactone) or Eudragit^® RS100 nanocapsules using Curcuma oil as the oil-based core. Until now, the effect of cationic nanocapsules on malaria has not been reported. A 2⁴ factorial design was adopted using, as independent variables, the concentration of Curcuma oil, presence of quinine, type of polymer, and aqueous surfactant. Diameter, zeta potential, and pH were the responses studied. The formulations were also evaluated for drug content, encapsulation efficiency, photostability, and antimalarial activity against Plasmodium berghei-infected mice. The type of polymer influenced all of the responses studied. Quinine-loaded Eudragit^® RS100 (F13) and PCL nanocapsules (F9), both with polysorbate 80 coating, showed nanometric particle size, positive zeta potential, neutral pH, high drug content, and quinine photoprotection ability; thus, these nanocapsules were selected for in vivo tests. Both formulations showed lower levels of parasitemia from the beginning of the experiment (5.78 ± 3.60 and 4.76 ± 3.46% for F9 and F13, respectively) and highest survival mean time (15.3 ± 2.0 and 14.9 ± 5.6 days for F9 and F13, respectively). F9 and F13 showed significant survival curve compared to saline, thus demonstrating that nanoencapsulation improved bioefficacy of QN and co-encapsulated curcuminoids, regardless of the surface charge.     

Design,semisynthesis and potent cytotoxic activity of novel 10-fluorocamptothecin derivatives

Fluorination is a well-known strategy for improving the bioavailability of bioactive molecules in the lead optimization phase of drug discovery projects. In an attempt to improve the antitumor activity of camptothecins (CPTs), novel 10-fluoro-CPT derivatives were designed, synthesized and evaluated for cytotoxicity against five human cancer cell lines (A-549, MDA-MB-231, KB, KB-VIN and MCF-7). All of the derivatives showed more potent in vitro cytotoxic activity than the clinical CPT-derived drug irinotecan against the tumor cell lines tested, and most of them showed comparable or superior potency to topotecan. Remarkably, compounds 16b (IC₅₀, 67.0 nM) and 19b (IC₅₀, 99.2 nM) displayed the highest cytotoxicity against the multidrug-resistant (MDR) KB-VIN cell line and merit further development as preclinical drug candidates for treating cancer, including MDR phenotype. Our study suggested that incorporation of a fluorine atom into position 10 of CPT is an effective method for discovering new potent CPT derivatives.     

Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO<Subscript>3</Subscript>NP) on 4T1 mouse breast cancer cell line

Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO₃NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO₃NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p < 0.05) number of apoptotic cells in both free DTX and DTX-CaCO₃NP groups. Cell cycle analysis showed cycle arrest at subG0 and G2/M phases in both treatment groups. SEM showed presence of cellular blebbing, while TEM showed nuclear fragmentation, apoptosis, and vacuolation in the treatment groups. Scratch assay showed lower (p < 0.05) closure in both free DTX and DTX-CaCO₃NP groups. The results from this study showed that DTX-CaCO₃NP has similar anticancer effects on 4T1 cells as free DTX, and since it has a slow release rate, it is a more preferred substitute for free DTX.     

Nitric oxide synthesis inhibition and cytotoxicity of Korean horse mussel Modiolus modiolus extracts on cancer cells in culture

The Korean horse mussel extract was purified and fractionated by a bioassay-guided purification step. The final fraction contained seven steroid and one polycyclic aromatic compounds, in which cholest-7-en-3-ol, (3β,5α)- (58.7 %) was a main component followed by ergosta-7,22dien-3-ol (3β,5α,22E) (13.0 %). This extract exhibited strong anti-inflammatory activity determined solely through the nitric oxide inhibition assay in a dose-dependant manner with the IC₅₀ value of 9.6 µg/mL and no cytotoxic effect on the macrophages. Moreover, it also exhibited strong cytotoxicity with the IC₅₀ values of 21.4, 36.4, and 37.1 µg/mL against AGS, DLD-1, and HeLa cells, respectively. These results indicated that the horse mussel extract might be a functional ingredient in the prevention of inflammation and human cancers.     

In vitro cytotoxicity screening of water-dispersible metal oxide nanoparticles in human cell lines

In this study, we present in vitro cytotoxicity of iron oxide (Fe₃O₄) and manganese oxide (MnO) using live/dead cell assay, lactate dehydrogenase assay, and reactive oxygen species detection with variation of the concentration of nanoparticles (5–500 μg/ml), incubation time (18–96 h), and different human cell lines (lung adenocarcinoma, breast cancer cells, and glioblastoma cells). The surface of nanoparticles is modified with polyethyleneglycol-derivatized phospholipid to enhance the biocompatibility, water-solubility, and stability under an aqueous media. While the cytotoxic effect was negligible for 18 h incubation even at highest concentration of 500 μg/ml, MnO nanoparticle represented higher level of toxicity than those of Fe₃O₄ and the commercial medical contrast reagent, Feridex after 2 and 4 day incubation time. However, the cytotoxicity of Fe₃O₄ is equivalent or better than Feridex based on the live/dead cell viability assay. The engineered MnO and Fe₃O₄ exhibited excellent stability compared with Feridex for a prolonged incubation time.     

In vitro anticancer activity of Spondias pinnata bark on human lung and breast carcinoma

Spondias pinnata, a commonly distributed tree in India, previously proven for various pharmacological properties and also reported for efficient anti-oxidant, free radical scavenging and iron chelating activity, continuing this, the present study is aimed to investigate the role of 70 % methanolic extract of S. pinnata bark (SPME) in promoting apoptosis in human lung adenocarcinoma cell line (A549) and human breast adenocarcinoma cell line (MCF-7). These two malignant cell lines and a normal cell line were treated with increasing concentrations of SPME and cell viability is calculated. SPME showed significant cytotoxicity to both A549 and MCF-7 cells with an IC₅₀ value of 147.84 ± 3.74 and 149.34 ± 13.30 μg/ml, respectively, whereas, comparatively no cytotoxicity was found in normal human lung fibroblast cell line (WI-38): IC₅₀ 932.38 ± 84.44 μg/ml. Flow cytometric analysis and confocal microscopic studies confirmed that SPME is able to induce apoptosis in both malignant cell lines. Furthermore, immunoblot result proposed the pathway of apoptosis induction by increasing Bax/Bcl-2 ratio in both cell types, which results in the activation of the caspase-cascade and ultimately leads to the cleavage of Poly adeno ribose polymerase. For the first time this study proved the anticancer potential of SPME against human lung and breast cancer by inducing apoptosis through the modulation of Bcl-2 family proteins. This might take S. pinnata in light to investigate it for further development as therapeutic anticancer source.