Higher Cytotoxic Effect Research Articles

Physical, biochemical, and biological characterization of olive-derived lipid nanovesicles for drug delivery applications

Extracellular vesicles (EVs) have shown great promise as drug delivery system (DDS). However, their complex and costly production limit their development for clinical use. Interestingly, the plant kingdom can also produce EV-like nanovesicles that can easily be isolated and purified from a large quantity of raw material at a high yield. In this study, olive-derived nanovesicles (ODNVs) were isolated from raw fruits using serial centrifugations and their physical and biological features characterized to demonstrate their promising potential to be used as a DDS. Nanotracking particle analysis indicated an average size of 109.5 ± 3.0 nm and yield of 1012 ODNVs/mL for the purest fraction. Microscopy imaging, membrane fluidity assay and lipidomics analysis showed the presence of a rich lipid bilayer that significantly varied between different sources of ODNVs but showed a distinct signature compared to human EVs. Moreover, ODNVs were enriched in PEN1 and TET8 compared to raw fruits, suggesting an extracellular origin. Interestingly, ODNVs size and yield stayed unchanged after exposure to high temperature (70 °C for 1 h), wide pH range (5–10), and 50–100 nm extrusion, demonstrating high resistance to physical and chemical stresses. This high resistance allowed ODNVs to stay stable in water at 4 °C for a month, or with the addition of 25 mM trehalose for long-term freezing storage. Finally, ODNVs were internalized by both 2D and 3D cell culture without triggering significant cytotoxicity and immunogenicity. Importantly, the anticancer drug doxorubicin (dox) could be loaded by passive incubation within ODNVs and dox-loaded ODNVs decreased cell viability by 90% compared to only 70% for free dox at the same concentration, indicating a higher efficiency of drug delivery by ODNVs. In addition, this high cytotoxicity effect of dox-loaded ODNVs was shown to be stable after a 2-week storage at 4 °C. Together, these findings suggested that ODNVs represent a promising candidate as drug nanocarrier for various DDS clinical applications, as demonstrated by their biocompatibility, high resistance to stress, good stability in harsh environment, and improvement of anticancer drug efficacy.

Investigation of The Effects of Extraction Polarity Change on the Bioactivity of Eruca vesicaria

Eruca vesicaria (arugula) plant is frequently used today as a daily food source that contains a rich variety of minerals and vitamins, especially vitamin C. It also contains a high percentage of phenolic compounds which are structures that plants develop to protect themselves from harmful organisms. Phenolic compounds found in plants are obtained by different extraction methods and have a high antioxidant effect. In this study, we report, anticancer activity extract from Eruca vesicaria against human prostate cancer cells (PC-3) in vitro. The phenolic substances contained in the plant were obtained in different concentrations by the extraction technique based on the polarity difference. HPLC and total phenol content were determined to perform extraction content analysis. According to in vitro MTT cell proliferation assay, it acted at high concentrations, regardless of polarity differences. The highest cytotoxic effect was observed in extract extracted with 50% ethanol concentration. It has been observed that it has an anticancer effect compared to the determination of total phenol content. Also, because of 24-hour MIC analysis, it shows antibacterial properties according to agent concentration. As a result of this study, it adds many new information to the literature, but also provides guidance for future research.

Molecular modeling and cytotoxic activity studies of oxirane-2-carboxylate derivatives

In this study, five 3-aryloxirane-2-carboxylate derivatives were prepared, and the antiproliferative activities of molecules were screened in lung and colon cancer cell lines. The results showed that molecules had antiproliferative activity on cancerous cells with IC50 values under 100 µM. Furthermore, all of the molecules were found to have a much higher cytotoxic effect than cisplatin in colon cancer cells. The interactions of the relatively active compounds to the crucial enzyme in cancer cell proliferation, cyclin-dependent kinase 1 (CDK1), were investigated using molecular docking. The stability of the resulting CDK1-compound complexes procured from the docking was also assessed through molecular dynamics (MD) simulations. Then, the binding affinity of compounds 2-3a and 2-3c to the target enzyme was computed by MMPBSA. The molecular docking study demonstrated that the two most active compounds could bind to the enzyme. The binding potential of 2-3a is anticipated to be higher as it had one more conventional hydrogen bond and a slightly lower binding energy than compound 2-3c. The MD simulation study exhibited that the two compounds formed a stable complex with the enzyme. On the other hand, the MMPBSA energy computation implicated a slightly higher binding affinity for compound 2-3c toward the enzyme. Furthermore, electrical and frontier molecular orbital analysis of all of the tested compounds was conducted by density functional theory (DFT) studies. Compound 2-3a is anticipated to be the most chemically stable as it gave the highest energy gap value in the DFT analysis.

Synthesis of bis-Chalcones Based on Green Chemistry Strategies and Their Cytotoxicity Toward Human MeWo and A375 Melanoma Cell Lines.

Chalcone is an aromatic ketone that forms the central core of many important biological compounds. Chalcone derivatives show various biological activities, especially anti-inflammatory, antibacterial, antioxidant, and anticancer activities, and also inhibit melanoma cell growth. In this study, we synthesized chalcone compounds with bis-chalcone's chemical structure under microwave (MW) and microwave-ultrasound (MW-US) conditions and compared them to chalcones produced using the classical synthesis method. All bis-chalcones were synthesized with terephthalaldehyde and an appropriate aromatic ketone as substrates in Claisen-Schmidt condensation. All the obtained compounds were tested regarding their roles as potential anticancer agents. The cytotoxic effect of the bis-chalcones against human MeWo and A375 melanoma cell lines was investigated through colorimetric MTT and SRB assays. The data were analyzed statistically. In the case of the synthesis of bis-chalcones, it was determined that the use of green conditions supported by the MW or MW-US factors led to an increase in the yield of the final products and a reduction in the reaction time compared to the classic method. The biological results showed the high cytotoxic effect of bis-chalcones. The present results show the compounds' high antiproliferative and cytotoxic potential, especially for the two selected bis-chalcone derivatives (3b and 3c), in particular, at concentrations of 50 μM-200 μM at 24, 48 h, and 72 h of incubation. The use of MW and US for the synthesis of bis-chalcones significantly improved the process compared to the classical method. The derivatives containing two hydroxy and two methoxy groups were the most effective against the tested cancer cells.

Effect of Amygdalin on Murine Melanoma Cancer Cell Line and Normal Human Fibroblast Cells

Background and Objectives: Melanoma is the most aggressive and fatal type of skin cancer caused by the uncontrolled proliferation of melanocytes. The ineffectiveness of existing therapies has encouraged researchers to use herbal medicines. Amygdalin is a natural cyanogenic glycoside that is found in fruits and seeds of different plants and has antiproliferative, antioxidant, and immune-regulating activities. In this study, we aim to evaluate the effect of amygdalin against murine melanoma cancer cell line and normal human fibroblast cells. Methods: The murine melanoma cancer cell line (B16F10) and human foreskin fibroblasts (HFF) cells were exposed to different concentrations of amygdalin and dacarbazine (a standard anticancer drug) for 24 and 48 hours. The half-maximal inhibitory concentration (IC50) of amygdalin was obtained using the MTT assay and analyzed in GraphPad Prism and Excel applications. Results: Amygdalin had a high cytotoxic effect on the melanoma cell line within 48 hours of exposure, which is comparable to the cytotoxicity of dacarbazine at the same time. Amygdalin had no cytotoxic effect on HFF cells, while dacarbazine caused a high toxicity on HFF cells. Conclusion: Amygdalin, by inhibiting the proliferation of cancer cells in a dose-dependent manner, may prevent the adverse effects of chemical drugs on healthy cells and can be an appropriate treatment option for melanoma.

In vitro toxicity of microalgae species of the phyla chlorophyta and ochrophyta in CHO-k1 and HEP G2 cells for potential use in human nutrition

Microalgae are a promising component to enhance human nutrition, but to date only a few species have been authorized to be used in human nutrition. In this study, the in vitro toxicity of eight novel microalgae strains (Botryococcus braunii, Chlorococcum novae-angliae, Microchloropsis salina, Myrmecia bisecta, Stichococcus sp. Tetraselmis suecica, Tetradesmus obliquus and Spongiochloris minor) selected for their potential for human nutrition was investigated. N-hexane, acetone, ethanol and aqueous extracts of the lyophilized biomass were tested in the CHO-k1 and HEP G2 cell lines at concentrations of up to 1.81 mg ml-1 extracted biomass per well. None of the tested microalgae extracts reached values defined as a significant cytotoxic effect (IC50 < 0.02 mg ml-1). The highest cytotoxic effects were measured for Stichococcus sp. in both cell lines with IC50 values of 0.17 mg ml-1 for the acetone extract in CHO-k1 cell culture and 0.18 mg ml-1 for the acetone extract in HEP G2 cell culture. Most cytotoxic effects occurred with the acetone and ethanol extracts, while the water and n-hexane extracts showed almost no measurable cytotoxic effects. Only Tetraselmis suecica showed no cytotoxic effect under the chosen conditions in both tested cell lines, marking this microalgae as particularly interesting for further investigations into its use in human nutrition.

Synthesis of New Pyrazolo[3,4-d]pyrimidine Derivatives: NMR Spectroscopic Characterization, X-Ray, Hirshfeld Surface Analysis, DFT, Molecular Docking, and Antiproliferative Activity Investigations.

Four new pyrazolo[3,4-d]pyrimidines (P1-P4) were successfully synthesized in good relative yields by reacting 3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ol with various alkylating agents (methyl iodide, propargyl bromide, and phenacyl bromide) at room temperature in DMF solvent, employing liquid-solid phase transfer catalysis. The P1-P4 structures were elucidated using NMR spectroscopy and X-ray diffraction. Intermolecular interactions in P1-P4 were analyzed via Hirshfeld surface analysis and 2D fingerprint plots. Geometrical parameters were accurately modeled by DFT calculations using the B3LYP hybrid functional combined with a 6-311++G(d,p) basis set. The antiproliferative activity of P1-P4 towards colorectal carcinoma (HCT 116), human hepatocellular carcinoma (HepG2), and human breast cancer (MCF-7) cell lines, along with one normal cell line (WI38) was investigated using the MTT assay and sunitinib as a reference. Compounds P1 and P2 exhibited antiproliferative activities comparable to the reference drug towards all tested cells, with an IC50 range of 22.7-40.75 µM. Both compounds also showed high selectivity indices and minimal cytotoxic effects on the normal cell line. Molecular docking revealed that the significant antiproliferative activity may attributed to the number and type of intermolecular hydrogen bonding established between pyrazolo[3,4-d]pyrimidines and DNA topoisomerase, a common target for various anticancer agents.

Cytotoxic activity properties of a benzimidazolium salt against lung, liver, and colon cancer cell lines

In this study, a known benzimidazolium salt was synthesized in two steps starting from N-phenyl-o-phenylenediamine. This compound was tested in vitro for 72 h against different cancer cell lines (A549 - lung cancer, HepG2 - liver cancer, DLD-1 - colon cancer) and to compare the activity of this compound with cisplatin, a widely used chemotherapeutic agent. The evaluation of compound 4 as a potential anticancer agent against different cancer types was achieved by examining the cytotoxic effects of this compound through IC50 values using the MTT method. It was found that compound 4 showed different activity depending on the cell type and had a high cytotoxic effect (IC50: 15.68 μM), especially against lung cancer cell line for 72 h incubation time.

Determination of the interactions of a schiff base with different targets via molecular docking and cytotoxic activity studies

The pyrimidine nucleus is a vital pharmacophore that exhibits excellent pharmacological activity. A Schiff base containing a pyrimidine nucleus was obtained in two steps. This compound was assessed on the human prostate (PC3) and liver (HepG2) cancer cell lines using the MTT method. The prepared compound 3 was determined to have a high cytotoxic effect towards prostate cancer with an IC50 value of 9.32 μM. Since experimental prostate and liver cancer studies were examined, the molecular docking study's target structures were determined accordingly. In molecular docking studies, compound 3 interacted in silico with the crystal structure of the human HER2 kinase domain (PDB Id: 3PP0), the crystal structure of VEGFR-2 (PDB Id: 4ASD), and the crystal structure of EGFR tyrosine kinase (PDB Id: 4HJO), respectively. As a result of these interactions, binding energy values were calculated, and binding modes were determined. Additional in vitro and in vivo experiments targeting other cancer cell lines will provide deeper insight into the anticancer spectrum of this compound and new studies on this compound will be planned in the following years. Furthermore, optimizing and studying such pyrimidine-based Schiff base compounds for improved selectivity and potency against prostate cancer is also considered to be valuable as it may increase the potential to capture potential drug candidates.

ROS-responsive glycol chitosan-linked prodrug nanoparticle as a nanoplatform for tumor chemo-photodynamic therapy

Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug via a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc in vitro. GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.

Enhancement of antimicrobial properties and cytocompatibility through silver and magnesium doping strategies on copper oxide nanocomposites

In the present study, silver (Ag), magnesium (Mg), and the various molar ratios of Ag:Mg-doped copper oxide nanocomposites (CuO NCs) were synthesized by the co-precipitation method. The CuO NC samples calcined at 500 °C were further analyzed for their morphological, structural, functional, and optical properties. Adding single and dual doping increased the pristine CuO band gap from 1.28 to 1.50 eV. The Ag and Mg metal peaks were revealed in the Fourier transform infrared (FTIR) analysis, while an elevated Mg band was observed in all Mg-doped samples in the Raman results. All CuO NCs showed a monoclinic crystalline structure, flake, and rod-like morphologies. Microbes of Bacillus subtilis, Shigella dysenteriae, and Candida albicans were tested against different concentrations of CuO NCs. Better results for all tested microbes were observed with the 2 mg concentration. The high cytotoxicity effect was observed in the pristine and Cu:Ag (94:6) sample, and other CuO NCs, which demonstrated over 80 % viability in RAW 246.7 cells at a concentration of 0.5 µg/ml. Remarkably, over 94 % cell viability at 0.5 µg/ml was achieved with the Cu:Ag:Mg (94:3:3) NCs ratio, owing to the synergistic effect of the ion-releasing ability of Cu2+, Ag2+, and Mg2+ ions. It possesses a distinctive high aspect ratio shape, is ion-releasing, and has excellent cytocompatibility. The suitability of the Cu:Ag:Mg (94:3:3) NCs ratio for addressing microbial challenges in healthcare is suggested by their distinct characteristics, indicating the promising potential for future biomedical applications.

Tomatidine, a Steroidal Alkaloid, Synergizes with Cisplatin to Inhibit Cell Viability and Induce Cell Death Selectively on FLT3-ITD+ Acute Myeloid Leukemia Cells.

Acute Myeloid Leukemia (AML) is a hematological cancer that frequently presents with a range of side effects and drug resistance during anticancer drug treatment. The current study aims to achieve increased efficacy by combining lower doses of cisplatin with increasing concentrations of tomatidine in AML cells to increase efficacy. Anti-proliferative effects of single and combination of cisplatin and tomatidine were assessed via MTT cell viability assay. The Annexin V/Propidium Iodide Double Staining method was used to measure the apoptotic effects of combined tomatidine and cisplatin treatment. Then, Western Blot analysis was performed to measure Poly (ADP-ribose) polymerase (PARP) and Caspase-3 protein expression levels. Cisplatin treatment with lower concentrations displayed high cytotoxic effects on AML cells, compared with tomatidine. The combination of the Inhibitory Concentration (IC) 20 value of cisplatin and increasing doses of tomatidine exhibited a significant decrease in cell viability relative to single treatments. The combination index analysis revealed a mild synergistic effect of cisplatin IC20 and varying tomatidine doses. The apoptosis induced when cisplatin was combined with 500 µM tomatidine by almost 20%, while the percentage of apoptosis in combination with 1 mM tomatidine was measured by 50% for both cell lines. The upregulation of proapoptotic cleaved-PARP (3.2 and 1.08-fold for THP-1 and MOLM-13, respectively) and downregulation in Caspase-3 (0.23 and 0.13-fold for THP-1 and MOLM-13, respectively) was detected. Together, the study indicated that when tomatidine combined with cisplatin on AML cell lines, a combinatorial anti-proliferative and apoptotic effect is observed. The combination of cisplatin with tomatidine may be a promising approach.

Specific antitumor activity of anti-CA125 CAR-T lymphocytes against CA125-positive and CA125-negative cells

Aim. To evaluate the antitumor efficacy of our developed drug based on cytotoxic T lymphocytes genetically modified with a chimeric antigen receptor (CAR) specific to the CA125 antigen in relation to both CA125-positive and CA125negative cell cultures.Materials and methods. We performed an in vitro study on CA125-positive human ovarian cancer cells (OVCAR-3, OVKATE) and CA125 negative cells (breast cancer MCF 7, embryonic kidney HEK293). Cytotoxic effects on tumor cells were evaluated after 0, 4, 8 and 24 hours using the 3’-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Lactate Dehydrogenase (LDH) tests. We also studied the changes in the number of cells “in real time” when exposed to transfected lymphocytes using the RTCA iCELLIgence device (ACEA Biosciences, USA). Lymphokineactivated killer (LAK) cells were used as a specificity control.Results. The study demonstrated that anti-CA125 CAR-T lymphocytes exhibited a pronounced cytotoxic effect on OVCAR-3 and OVKATE cell cultures, exceeding the effect of LAK by 1.3 times. The cell population in the experimental samples decreased by 70 ± 4%, which exceeded the LAK effect by 9 ± 8.2%. With regard to the MCF-7 cell line, the cytotoxic effect of anti-CA125 CAR-T lymphocytes was minimal as evidenced by a 25.8% decrease in the relative number of live cells in comparison to the LAK cytotoxicity of 68%. Real-time monitoring of cell proliferation and viability proved a high specific cytotoxic effect of anti-CA125 CAR-T lymphocytes against tumor cultures expressing CA-125, while inferior to LAK in cultures not expressing CA125 (MCF-7, HEK293).Conclusions. The use of anti-CA125 CAR-T lymphocytes against CA125-positive tumor cell lines OVCAR-3 and OVKATE demonstrated a pronounced specific cytotoxic effect exceeding the cytotoxic effect of LAK, which was not achieved against CA125-negative MCF-7 and HEK293 cells.

Antioxidant Properties of Lippia alba Essential Oil: A Potential Treatment for Oxidative Stress-Related Conditions in Plants and Cancer Cells.

Lippia alba (Mill.) N.E.Br. ex Britton and P. Wilson is used in folk medicine of Central and South America for its biological activities: i.e., antifungal, antibacterial, antiviral, and anti-inflammatory. Based on ethnopharmacological information and the increasing interest in this species, this work aimed to test a possible wide use of its essential oil (EO) in pharmaceutical and horticultural applications. Therefore, we focused the attention on the antioxidant activity of the oil as a possible tool to overcome the oxidative stress in both applications. For this purpose, we have chosen three aggressive breast cancer cell lines and two horticultural species (Solanum lycopersicum L. and Phaseolus acutifolius L.) that are very sensitive to salt stress. We determined the antioxidant activity of L. alba EO through the quantification of phenols and flavonoids. Regarding tomato and bean plants under salt stress, L. alba EO was used for the first time as a seed priming agent to enhance plant salt tolerance. In this case, the seed treatment enhanced the content of phenolic compounds, reduced power and scavenger activity, and decreased membrane lipid peroxidation, thus mitigating the oxidative stress induced by salt. While in breast cancer cells the EO treatment showed different responses according to the cell lines, i.e., in SUM149 and MDA-MB-231 the EO decreased proliferation and increased antioxidant activity and lipid peroxidation, showing high cytotoxic effects associated with the release of lactate dehydrogenase, vice versa no effect was observed in MDA-MB-468. Such antioxidant activity opens a new perspective about this essential oil as a possible tool to counteract proliferation in some cancer cell lines and in horticulture as a seed priming agent to protect from oxidative damage in crops sensitive to salinity.

New Smoothened ligands based on the purine scaffold as potential agents for treating pancreatic cancer

Aberrant activation of the Hedgehog (Hh) signalling pathway has been associated with the development and progression of pancreatic cancer. For this reason, blockade of Hh pathway by inhibitors targeting the G protein-coupled receptor Smoothened (SMO) has been considered as a therapeutic target for the treatment of this cancer. In our previous work, we obtained a new SMO ligand based on a purine scaffold (compound I), which showed interesting antitumor activity in several cancer cell lines. In this work, we report the design and synthesis of 17 new purine derivatives, some of which showed high cytotoxic effect on Mia-PaCa-2 (Hh-dependent pancreatic cancer cell lines) and low toxicity on non-neoplastic HEK-293 cells compared with gemcitabine, such as 8f, 8g and 8h (IC50 = 4.56, 4.11 and 3.08 μM, respectively). Two of these purines also showed their ability to bind to SMO through NanoBRET assays (pKi = 5.17 for 8f and 5.01 for 8h), with higher affinities to compound I (pKi = 1.51). In addition, docking studies provided insight the purine substitution pattern is related to the affinity on SMO. Finally, studies of Hh inhibition for selected purines, using a transcriptional functional assay based on luciferase activity in NIH3T3 Shh-Light II cells, demonstrated that 8g reduced GLI activity with a IC50 = 6.4 μM as well as diminished the expression of Hh target genes in two specific Hh-dependent cell models, Med1 cells and Ptch1−/− mouse embryonic fibroblasts. Therefore, our results provide a platform for the design of SMO ligands that could be potential selective cytotoxic agents for the treatment of pancreatic cancer.

An investigation of the dose-dependent safety of bemiparin sodium: A cell culture study

Aim: Fibroblasts are common cells in subcutaneous tissue and they have an important role on healing process. Although patients who are receiving first-generation low molecular weight heparins are more likely to experience skin responses, there is no study evaluating the effect of bemiparin sodium on subcutaneous fibroblasts following administration. In the present study, we aimed to evaluate the effects of bemiparin sodium on fibroblast cell viability in cell culture model. Material and Methods: The L929 cells were incubated for 12 hours in 96-well culture dishes. Fresh medium containing different concentrations of bemiparin was added in five different concentrations (Dilution I: 3,500 IU; Dilution II: 1,750 IU; Dilution III: 875 IU; Dilution IV: 437.5 IU; Dilution V: 218.75 IU). A control group was established with drug-free culture medium. Cell viability analysis was performed after 48 hours of incubation by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. The change in cell morphology was examined at each dilution by direct and acridine orange/propidium iodide staining. Results: The highest cytotoxic effect was observed in dilution I compared to the control group (p<0.05). There is a clear deviation from the fibroblastic morphology of the cells in dilution I. The cells have a round morphology with degeneration and nuclear condensation. Conclusion: Although it seems that high doses of bemiparin may have a negative effect on fibroblast cells in subcutaneous tissue, it can be considered that the cytotoxic effects of high concentrations of the drug at the application site will not be clinically significant due to using a single dose per day.

Exploring the Biosafety Potential of Haberlea rhodopensis Friv. In Vitro Culture Total Ethanol Extract: A Comprehensive Assessment of Genotoxicity, Mitotoxicity, and Cytotoxicity for Therapeutic Applications.

The escalating elderly population worldwide has prompted a surge of interest in longevity medicine. Its goal is to interfere with the speed of ageing by slowing it down or even reversing its accompanying effects. As a field, it is rapidly growing and spreading into different branches. One of these is the use of nutraceuticals as anti-ageing drugs. This field is gaining massive popularity nowadays, as people are shifting towards a more natural approach to life and seeking to use natural products as a source of medicine. The present article focuses on the cellular effect of Haberlea rhodopensis Friv. in vitro culture total ethanol extract (HRT), produced by a sustainable biotechnological approach. The extract showed a similar phytochemical profile to plant leaf extract and was rich in primary bioactive ingredients-caffeoyl phenylethanoid glycosides, myconoside, and paucifloside. This study examined the biosafety potential, cytotoxicity, genotoxicity, and mitochondrial activity of the extract using in vitro cultures. The results showed high cell survival rates and minimal cytotoxic effects on Lep3 cells, with no induction of reactive oxygen species nor genotoxicity. Additionally, the extract positively influenced mitochondrial activity, indicating potential benefits for cellular health. The results are promising and show the beneficial effect of HRT without the observation of any adverse effects, which sets the foundation for its further testing and potential therapeutic applications.

Organotin complexes with Schiff’s base ligands: insights into their cytotoxic effects on lung cancer cells

AbstractOrganotin(IV) complexes can be used in chemotherapy due to its lipophilicity which can be affected by the availability of Sn coordination bond and bond stabilization between ligand and Sn(IV). In this study, three types of tri-organotin(IV) complexes which are, Ph3SnL, Me3SnL, and Bu3SnL derived from Schiff base ligand were synthesized by the reaction of methyl dopa with p-dimethyaminobenzaldehyde. All prepared complexes were charechterised using nuclear magnetic resonance (1H NMR, 13C NMR, and 119Sn NMR. The 1H NMR). The results confirm the coordination of the organotin(IV) moieties to the ligand. The cytotoxicity of tri-organotin(IV) complexes was evaluated against the A549 human lung cancer cell using MTT assay. Ph3SnL showed a high cytotoxic effect among othger complexes, Bu3SnL also showed a significant cytotoxic effect, while Me3SnL demonstrated a relatively lower effects. These findings highlight the potential of the tri-organotin(IV) complexes, particularly Ph3SnL and Bu3SnL, as promising candidates for further modification as anticancer agents. The results obtained from this study can be used to understand the structure–activity of organotin(IV) complexes and their applications as anti-cancer activity.

Development of Graphene Oxide-Based Anticancer Drug Combination Functionalized with Folic Acid as Nanocarrier for Targeted Delivery of Methotrexate.

Graphene has become a prominent material in cancer research in recent years. Graphene and its derivatives also attract attention as carriers in drug delivery systems. In this study, we designed a graphene oxide (GO)-based methotrexate (MTX)-loaded and folic acid (FA)-linked drug delivery system. MTX and FA were bound to GO synthesized from graphite. MTX/FA/GO drug delivery system and system components were characterized using Fourier transform infrared spectroscopy (FTIR), differential calorimetric analysis (DSC), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential analysis, and dimension measurement (DLS) studies. SEM and TEM images confirmed the nanosheet structure of GO synthesized from graphite, and it was shown that MTX/FA binding to GO transformed the two-dimensional GO into a three-dimensional structure. FTIR and DSC graphs confirmed that oxygen atoms were bound to GO with the formation of carboxylic, hydroxyl, epoxide, and carbonyl groups as a result of the oxidation of graphite, and GO was successfully synthesized. Additionally, these analyses showed that MTX and FA bind physicochemically to the structure of GO. The in vitro Franz diffusion test was performed as a release kinetic test. The release kinetics mathematical model and correlation coefficient (R2) of MTX-loaded GO/FA nanomaterials were found to be the Higuchi model and 0.9785, respectively. Stiffness analyses showed that adding FA to this release system facilitated the entry of the drug into the cell by directing the system to target cells. As a result of the stiffness analyses, the stiffness values of the control cell group, free MTX, and MTX/FA/GO applied cells were measured as 2.34 kPa, 1.87 kPa, and 1.56 kPa, respectively. According to these results, it was seen that MTX/FA/GO weakened the cancer cells. Combined use of the MTX/FA/GO drug delivery system had a higher cytotoxic effect than free MTX on the MDA-MB-231 breast cancer cell line. The results showed that the synthesized MTX/FA/GO material has promising potential in cancer cell-specific targeted therapy for MTX as a drug delivery system.

Magnetic alginate core-shell nanoparticles based on Schiff-base imine bonding for pH-responsive doxorubicin delivery system

This research describes the development of a novel pH-responsive drug delivery system (DDS) based on sodium alginate (SA) and magnetic nanoparticles (MNPs) for cancer treatments. One possible approach to creating a wide variety of functional nanoparticles is to graft functional materials onto magnetite nanoparticles. In this study, we demonstrate the effective alteration of Fe3O4 nanoparticles using the alginate dialdehyde (ADA) group through a Schiff-Base imine reaction toward synthesizing Fe3O4@SiO2@APTMS@ADA (FSA@ADA) nanocarrier (NC). doxorubicin (DOX) as an anticancer drug was loaded (about 93 % drug loading capacities) on the FSA@ADA NC through chemical and physical interactions. doxorubicin (DOX) as an anticancer drug was loaded (about 93 % drug loading capacities) on the FSA@ADA NC through chemical and physical interactions. The synthesized nanocarriers were thoroughly characterized by various techniques, including FT-IR, FE-SEM, EDX-MAP, TEM, XRD, VSM, TGA, and 1HNMR. In vitro DOX release studies showed a pH-dependent manner and its release rate is lower (< 15 %) at 7.4 than pH 5 (about 75 %) over 25 days. Cytotoxicity results showed good biocompatibility for blank FSA@ADA (over about 85 % cell viability), whereas DOX-loaded FSA@ADA NCs had higher cytotoxic effects (IC50 value: ∼6 µg/mL) as a result of the controlled release of DOX into HeLa cells. Results showed that the magnetic core-shell FSA@ADA/DOX NC has the potential to be used as a targeted stimuli-responsive drug for cancer treatment.