scholarly journals Cytotoxicity of Taxol in Combination with Vincristine and Vinblastine Against A375 Cell Line

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Mohammad Zandi
Keyword(s):  
Side Effects ◽  
Therapeutic Option ◽  
Inhibitory Effect ◽  
In Vitro Cytotoxicity ◽  
In Vitro Toxicity ◽  
Human Malignant Melanoma ◽  
Promising Strategy ◽  
A375 Cell Line ◽  
A375 Cells

Background: Annually, various types of cancer cause thousands of deaths globally, and identifying an appropriate therapeutic option for these disorders is of crucial importance. Side effects of anticancer drugs can be reduced through the promising strategy of combination therapy. Objectives: The present paper has investigated the in vitro cytotoxicity of Taxol, carboplatin, vinblastine, and vincristine alone and in combination against human malignant melanoma A375 cells and non-cancerous fibroblast HU2 cells to examine the possible side effects of the drugs. Methods: The cells were subjected to the examined compounds for 48 h, and the MTT test was conducted to evaluate the cytotoxicity. Results: The results indicated that the most significant effect was related to 120 μg/mL vincristine and 7.5 μg/mL Taxol+ vincristine treatments, with the survival amounts of 24 ± 0.6 and 28 ± 0%, respectively. In addition, the best 50% inhibitory effect was found to be related to Taxol + vincristine, vinblastine, and Taxol+ vinblastine treatments at the concentrations of 0.04, 2.2, and 3.4 μg/mL, respectively. Conclusions: According to the findings of in vitro toxicity, the evaluated complexes are not cytotoxic against human fibroblast HU2 cells. Also, the most significant effect on A375 cells was associated with vincristine treatment. No synergistic reaction was recorded among the different combinations of drugs based on the calculated CI values.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

The Effect of Phase Transition Temperature on Therapeutic Efficacy of Liposomal Bortezomib

2020 ◽  
Vol 20 (6) ◽  
pp. 700-708
Author(s):  
Mitra Korani ◽  
Sara Nikoofal-Sahlabadi ◽  
Amin R. Nikpoor ◽  
Solmaz Ghaffari ◽  
Hossein Attar ◽  
...  
Keyword(s):  
Side Effects ◽  
Cell Line ◽  
Therapeutic Efficacy ◽  
Drug Loading ◽  
Particle Diameter ◽  
In Vitro Cytotoxicity ◽  
Liposomal Formulations ◽  
Cytotoxicity Studies ◽  
Anti Tumor Activity

Aims: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. Background: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. Objective: Evaluating anti-tumor activity of bortezomib liposomal formulations. Methods: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. Result: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. Conclusion: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.

scholarly journals Synthesis of Gold Nanoparticles by Using Green Machinery: Characterization and In Vitro Toxicity

Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 808
Author(s):  
Ahmed Al Saqr ◽  
El-Sayed Khafagy ◽  
Ahmed Alalaiwe ◽  
Mohammed F. Aldawsari ◽  
Saad M. Alshahrani ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Average Particle Size ◽  
In Vitro Cytotoxicity ◽  
In Vitro Toxicity ◽  
Cervical Cancer Cell Line ◽  
Average Particle ◽  
Anticancer Activities ◽  
Tem Analysis ◽  
Benincasa Hispida

Green synthesis of gold nanoparticles (GNPs) with plant extracts has gained considerable interest in the field of biomedicine. Recently, the bioreduction nature of herbal extracts has helped to synthesize spherical GNPs of different potential from gold salt. In this study, a fast ecofriendly method was adopted for the synthesis of GNPs using fresh peel (aqueous) extracts of Benincasa hispida, which acted as reducing and stabilizing agents. The biosynthesized GNPs were characterized by UV–VIS and Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering. In addition, the in vitro antibacterial and anticancer activities of synthesized GNPs were investigated. The formation of gold nanoparticles was confirmed by the existence of a sharp absorption peak at 520 nm, corresponding to the surface plasmon resonance (SPR) band of the GNPs. TEM analysis revealed that the prepared GNPs were spherical in shape and had an average particle size of 22.18 ± 2 nm. Most importantly, the synthesized GNPs exhibited considerable antibacterial activity against different Gram-positive and Gram-negative bacteria. Furthermore, the biosynthesized GNPs exerted remarkable in vitro cytotoxicity against human cervical cancer cell line, while sparing normal human primary osteoblast cells. Such cytotoxic effect was attributed to the increased production of reactive oxygen species (ROS) that contributed to the damage of HeLa cells. Collectively, peel extracts of B. hispida can be efficiently used for the synthesis of GNPs, which can be adopted as a natural source of antimicrobial and anticancer agent.

scholarly journals TERT Promoter Revertant Mutation Inhibits Melanoma Growth through Intrinsic Apoptosis

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 141
Author(s):  
Yanbing Wang ◽  
Yiwu Chen ◽  
Chang Li ◽  
Zhiwei Xiao ◽  
Hongming Yuan ◽  
...  
Keyword(s):  
Therapeutic Option ◽  
B Cell Lymphoma ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Catalytic Core ◽  
Tert Promoter ◽  
Human Telomerase ◽  
Mutant Cells

Human telomerase is a specialized DNA polymerase whose catalytic core includes both TERT and human telomerase RNA (hTR). Telomerase in humans, which is silent in most somatic cells, is activated to maintain the telomere length (TEL) in various types of cancer cells, including melanoma. In the vast majority of tumor cells, the TERT promoter is mutated to promote proliferation and inhibit apoptosis. Here, we exploited NG-ABEmax to revert TERT -146 T to -146 C in melanoma, and successfully obtained TERT promoter revertant mutant cells. These TERT revertant mutant cells exhibited significant growth inhibition both in vitro and in vivo. Moreover, A375−146C/C cells exhibited telomere shortening and the downregulation of TERT at both the transcription and protein levels, and migration and invasion were inhibited. In addition, TERT promoter revertant mutation abrogated the inhibitory effect of mutant TERT on apoptosis via B-cell lymphoma 2 (Blc-2), ultimately leading to cell death. Collectively, the results of our work demonstrate that reverting mutations in the TERT promoter is a potential therapeutic option for melanoma.

Efficacy of Different Hexacyanoferrates(II) in Inhibiting the Intestinal Absorption of Radiocaesium in Rats

1990 ◽  
Vol 45 (6) ◽  
pp. 676-680 ◽  
Author(s):  
Bernd Dresow ◽  
Peter Nielsen ◽  
Hellmuth C. Heinrich
Keyword(s):  
Side Effects ◽  
Binding Capacity ◽  
Domestic Animals ◽  
Inhibitory Effect ◽  
Time Interval ◽  
Oral Doses ◽  
Severe Nuclear Accident ◽  
Cobalt And Nickel

Abstract The inhibitory effect of various oral doses of different hexacyanoferrate(II) compounds (HCF) and the influence of the time interval of HCF-administration on intestinal 134Cs-absorption was studied in rats. Optimum inhibition was obtained by administration of HCF together with or 2 min before oral 134Cs loading. Using appropriate low amounts (0.1 -0.5 mg) of the different HCF compounds, the inhibitory effect increased in the sequence KZnHCF < KCuHCF < FeHCF < KCoHCF = KNiHCF < NH4FeHCF = KFeHCF . Oral administration of 5 mg (0.5 mg) of KFeHCF , together with 134CsCl loading, reduces 134Cs-absorption from 41 % (control) to 0.8% (2.8%). Zinc-, copper-, cobalt, and nickel hexacyanoferrates(II), despite showing a high caesium sorption capacity in vitro, were less effective in rats and are not suited for in vivo application, also because they may produce toxic side effects. As a consequence, the orally administered colloidal-soluble iron (III) hexacyanoferrates(II) (NH4Fe[Fe(CN)6] and KFe[Fe(CN)6]) have to be considered as the most valuable countermeasure against radiocaesium absorption for humans and domestic animals in the case of a severe nuclear accident in the future. Manganese oxide, a non-hexacyanoferrate(II) compound with known in vitro caesium binding capacity, showed no inhibitory effect on radiocaesium absorption in rats.

scholarly journals In Vitro Toxicity Study of a Porous Iron(III) Metal‒Organic Framework

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1211 ◽  
Author(s):  
Gongsen Chen ◽  
Xin Leng ◽  
Juyuan Luo ◽  
Longtai You ◽  
Changhai Qu ◽  
...  
Keyword(s):  
Metal Organic Framework ◽  
Drug Carrier ◽  
In Vitro Cytotoxicity ◽  
In Vitro Toxicity ◽  
Porous Iron ◽  
Dapi Staining ◽  
Toxicological Assessment ◽  
Metal Organic ◽  
Organic Framework

A MIL series metal‒organic framework (MOF), MIL-100(Fe), was successfully synthesized at the nanoscale and fully characterized by TEM, TGA, XRD, FTIR, DLS, and BET. A toxicological assessment was performed using two different cell lines: human normal liver cells (HL-7702) and hepatocellular carcinoma (HepG2). In vitro cytotoxicity of MIL-100(Fe) was evaluated by the MTT assay, LDH releasing rate assay, DAPI staining, and annexin V/PI double staining assay. The safe dose of MIL-100(Fe) was 80 μg/mL. It exhibited good biocompatibility, low cytotoxicity, and high cell survival rate (HL-7702 cells’ viability >85.97%, HepG2 cells’ viability >91.20%). Therefore, MIL-100(Fe) has a potential application as a drug carrier.

Protein Precipitation In Vitro as a Measure of Chemical-induced Cytotoxicity: An EDIT Sub-programme

2001 ◽  
Vol 29 (3) ◽  
pp. 309-324
Author(s):  
Apolonia Novillo ◽  
Barbro Ekwall ◽  
Argelia Castaño
Keyword(s):  
Cell Lines ◽  
Human Cell ◽  
Exposure Period ◽  
Negative Control ◽  
In Vitro Cytotoxicity ◽  
Protein Precipitation ◽  
In Vitro Toxicity ◽  
Human Cell Lines ◽  
Response Curves

As a priority area of the Evaluation-Guided Development of In Vitro Toxicity and Toxicokinetic Tests (EDIT) programme, an in vitro protein precipitation (PP) assay was used on the 50 reference chemicals of the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) project, to confirm and extend the MEIC results. Dose–response curves were generated for only 30 of the chemicals, and the concentrations causing 10% (EC10) and 50% (EC50) protein precipitation versus the positive control were chosen as endpoints. The number of chemicals with a positive response increased to 46 when a new endpoint, the minimum effect concentration (MEC) that induces protein precipitation with respect to the negative control, was used. When the results were correlated with in vitro cytotoxicity in human cell lines, a similarly good correlation was found between the various endpoints of the PP assay at 5 hours and the 24-hour IC50 average cytotoxicity in human cell lines, even though the number of chemicals included in the correlation was larger for the MEC. Using the prediction error, the endpoint that gave the best correlation between the PP assay and human cell cytotoxicity was once more found to be the 5-hour MEC, and this was chosen for the PP assay. The sensitivity of the PP assay is lower than that of the in vitro cell-line cytotoxicity assay, possibly due to its shorter exposure period and because precipitation is the ultimate event in the sequence of a protein disturbance. It is expected that earlier denaturation steps would give better sensitivity. However, this simple, inexpensive and rapid assay could be useful in the early stages of testing chemicals.

scholarly journals Invitro Toxicity of Binary Mixtures of Glyphosate and 2, 2 Dichlorovinyl Dimethyl Phosphate on Bacterial Isolates

2021 ◽  
pp. 36-48
Author(s):  
C. O. Anuniru ◽  
J. N. Ogbulie ◽  
C. C. Opurum ◽  
E. S. Asiwe
Keyword(s):  
Binary Mixtures ◽  
Bacterial Species ◽  
Aquatic Organisms ◽  
Inhibitory Effect ◽  
In Vitro Toxicity ◽  
Triphenyltetrazolium Chloride ◽  
Dimethyl Phosphate ◽  
Low Concentrations ◽  
Artificial Electron Acceptor

The in vitro toxicity of glyphosate (Gly) and 2, 2 Dichlorovinyl dimethyl phosphate (DDVP) single compound and binary mixtures was assessed against Pseudomonas sp. and Bacillus sp. isolated from Otamiri River, Imo state, Nigeria was investigated. The toxicity response was assessed using the inhibitory effect of the single and binary mixtures on isolates dehydrogenase activity; and 2,3,5 triphenyltetrazolium chloride (TTC) was used as the artificial electron acceptor. The binary mixtures were composed using fixed ratios of glyphosate and 2, 2 Dichlorovinyl dimethyl phosphate in ratios of 20% Gly:80% DDVP, 40% Gly: 60% DDVP, 50% Gly: 50% DDVP, 60% Gly: 40% DDVP and 80% Gly: 20% DDVP. Results obtained showed that the isolates exhibited different degrees of logistic and sigmoidal toxicity trends with areas of hormesis at low concentrations of the toxicants. Furthermore, isobolographic analysis on the toxic interaction of the mixtures presented both synergism and antagonism, based on the relative ratio of the component mixtures. Increasing concentration of glyphosate in the binary mixture caused a shift in the interaction effect from antagonism to synergism. Our findings showed that isolates exhibited tolerance to glyphosate and 2,2 dichlorovinyl dimethyl phosphate and their binary mixtures exposure at concentration range of 0-1000mg/L; above which has deleterious effects on the aquatic organisms. It is evident that there are considerable differences in pesticide sensitivity among the bacterial species and that the presence of glyphosate and 2, 2-dichlorovinyl dimethyl phosphate in the aquatic environment may present toxicological risk to microbial diversity.

scholarly journals Antibacterial and Anti-Virulence Effects of Furazolidone on Trueperella Pyogenes and Pseudomonas Aeruginosa

2021 ◽  
Author(s):  
Qin Chen ◽  
Kelei Zhao ◽  
Heyue Li ◽  
Kanghua Liu ◽  
Jing Li ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Basis ◽  
Inhibitory Effect ◽  
Signal Molecules ◽  
Musk Deer ◽  
Trueperella Pyogenes ◽  
Screening Experiments ◽  
Promising Strategy ◽  
Biofilm Production

Abstract Background: Trueperella pyogenes and Pseudomonas aeruginosa are two important bacterial pathogens closely relating to the occurrence and development of forest musk deer respiratory purulent disease. Although T. pyogenes is the causative agent of the disease, the subsequently invaded P. aeruginosa will predominate the infection by producing a substantial amount of quorum-sensing (QS)-controlled virulence factors, and co-infection of them usually creates serious difficulties for veterinary treatment. In order to find a potential drug that targets both T. pyogenes and P. aeruginosa, the antibacterial and anti-virulence capacities of 55 compounds, which have similar core structure to the signal molecules of P. aeruginosa QS system, were tested in this study. By performing a series of in vitro screening experiments to assess the effects of these compounds.Results: We identified that furazolidone could significantly inhibit the growth of mono-cultured T. pyogenes or in the co-culture with P. aeruginosa. Although the growth of P. aeruginosa could also be moderately inhibited by furazolidone, the results of phenotypic identification and transcriptomic analysis further revealed that furazolidone had remarkable inhibitory effect on the biofilm production, motility, and QS system of P. aeruginosa. Moreover, furazolidone could efficiently protect Caenorhabditis elegans from P. aeruginosa infection under both fast-killing and slow-killing conditions.Conclusions: This study reports the antibacterial and anti-virulence abilities of furazolidone on T. pyogenes and P. aeruginosa, and provides a promising strategy and molecular basis for the development of novel anti-infectious drugs to dealing with forest musk deer purulent disease, or other diseases caused by T. pyogenes and P. aeruginosa co-infection.

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