Cancer A549 Cells Research Articles

Formulation and Evaluation of Lipid/Soluplus-Stabilized Nanocrystals of Paclitaxel and Bosutinib for a Synergistic Effect in Non-Small Cell Lung Cancer Therapy.

Tyrosine kinase inhibitors have been employed for the treatment of lung cancer, owing to their role in regulating irregulated pathways or mutated genes. Bosutinib, a nonreceptor tyrosine kinase, has been recently investigated for lung cancer treatment. Bosutinib can also be used with paclitaxel as a combinatorial approach to receive a synergistic effect for the effective management of lung cancer. Furthermore, the nanocrystals of each can also be prepared and in combination can produce a more pronounced impact than the drug combination. Herein, the prepared Soluplus/lipid-stabilized nanocrystals of paclitaxel and bosutinib were rod to cubic in shape of about 150-250 nm. The nanocrystals were stable, provided controlled drug release, and exhibited a higher aerosolization performance. The nanocrystal combination demonstrated higher anticancer activity than the drug combination synergy against A549 cancer cells. The nanocrystals increased the level of cellular internalization in cancer cells, thereby inducing higher ROS generation and apoptosis of cancer cells. Furthermore, the lipid/Soluplus-stabilized nanocrystals exhibited higher translocation potential compared with only Soluplus-stabilized nanocrystals. The nanocrystals administered intratracheally showed a lower drug distribution to other organs, with prolonged drug retention in the lungs, suggesting the higher efficacy of developed nanocrystals in targeting the lungs. In conclusion, lipid-modified nanocrystals can be a novel approach for the effective management of lung cancer.

Mannose functionalized small molecule nanodrug self-assembled from amphiphilic prodrug connected by disulfide bonds for synergistic cancer chemotherapy and photodynamic/photothermal therapy.

Compared to conventional nanocarrier-based drug delivery technology, small-molecule-assembled nanomaterials provide various advantages, including higher drug loading efficiency, lower excipient-related toxicity, and a simpler formulation process. Our research constructed a mannonse-modified small-molecule-assembled nanodrug for synergistic photodynamic/chemotherapy against A549 cancer cells. The hydrophobic hypoxic-activated agent tirapazamine (TPZ) and a hydrophilic fluorescence probe Cyanine 3 (Cy3) constitute this amphiphilic prodrug via a glutathione (GSH)-responsive linkage, which could self-assemble into stable nanoparticles (NPs) and encapsulate a newly synthesized photosensitizer (SeBDP). To enhance the tumor targeting capability, we introduced a tumor-targeted nanodrug SeBDP@TPZ-S-S-Cy/Man NPs by co-assembling mannose-modified lipid (DSPE-PEG-Man). The GSH-responsive linkage of TPZ-S-S-Cy can be rapidly cleaved by GSH to release the therapeutic agents and fluorescent molecule. The released SeBDP generate reactive oxygen species (ROS) to specifically kill cancer cells and elevate hypoxia, thereby enhancing the cytotoxicity of TPZ. SeBDP@TPZ-S-S-Cy/Man NPs exhibited high selectivity and efficiency for in vivo combination therapy without adverse effects to normal tissues. Our findings demonstrate that SeBDP@TPZ-S-S-Cy/Man NPs have great potential for enhancing cancer treatment both in vitro and in vivo by combining an oxygen depletion prodrug with a hypoxia-activated antitumor agent. Thus, the GSH-sensitive self-assembled nanodrug from an amphiphilic hypoxia-activated prodrug, could serve as a potential drug carrier in targeted synergistic cancer therapy.

Y2O3NPs induce selective cytotoxicity, genomic instability, oxidative stress and ROS mediated mitochondrial apoptosis in human epidermoid skin A-431 Cancer cells

Yttrium oxide nanoparticles (Y2O3NPs) have emerged as a promising avenue for cancer therapy, primarily due to their distinctive properties that facilitate selective targeting of cancer cells. Despite their potential, the therapeutic effects of Y2O3NPs on human epidermoid skin cancer remain largely unexplored. This study was thus conducted to investigate the impact of Y2O3NPs on both human skin normal and cancer cells, with an emphasis on assessing their cytotoxicity, genotoxicity, and the mechanisms underlying these effects. Cell viability and apoptosis induction were assessed using the Sulforhodamine B and chromatin diffusion assay, respectively. Reactive oxygen species (ROS) level, mitochondrial membrane potential integrity, oxidative stress markers and expression level of apoptotic and mitochondrial genes were also estimated. Our findings highlight the selective and significant cytotoxicity of Y2O3NPs against human epidermoid A-431 cancer cells. Notably, exposure to five Y2O3NPs concentrations (0.1, 1, 10, 100 and 1000 µg/ml) resulted in a high concentration-dependent reduction in cell viability and a corresponding increase in cell death observed 72 h post-treatment specifically in A-431 cancer cells, while normal skin fibroblast (HSF) cells exhibited minimal toxicity. When A-431 cancer cells were treated with the half-maximal inhibitory concentration (IC50) of Y2O3NPs for 72 h, a significant increase in ROS generation was noted. This led to oxidative stress, along with severe damage to genomic DNA and mitochondrial membrane potential, triggering substantial apoptosis. Furthermore, a concurrent significant upregulation of apoptotic p53 and mitochondrial ND3 genes was observed, coupled with a notable decrease in the anti-apoptotic Bcl2 gene expression.Overall, Y2O3NPs demonstrate considerable promise as a therapeutic agent for skin epidermoid cancer due to their ability to selectively target and induce cytotoxic effects in A-431 cancer cells, all while causing minimal harm to normal HSF cells. This selective cytotoxicity appears to be associated with Y2O3NPs’ ability to induce excessive ROS production and subsequent oxidative stress, leading to significant genomic DNA fragmentation, loss of mitochondrial permeability, and alterations in apoptotic and mitochondrial genes’ expression, ultimately promoting apoptosis in A-431 cancer cells. These findings establish a foundation for further research into the utilization of Y2O3NPs in targeted cancer therapies and underscore the necessity for ongoing investigation into their safety and efficacy in clinical applications.

Royal Jelly's Strong Selective Cytotoxicity Against Lung Malignant Cells and Macromolecular Alterations in Cells Observed by FTIR Spectroscopy.

Several nutraceuticals, food, and cosmetic products can be developed using royal jelly. It is known for its potential health benefits, including its ability to boost the immune system and reduce inflammation. It is rich in vitamins, minerals, and antioxidants, which can improve general health. Royal jelly (RJ) is also being studied as a potential therapeutic agent for cancer and other chronic diseases. It is effective in reducing tumor growth and stimulating immunity. In this study, we investigated the effects of royal jelly on cancerous A549 cells and healthy MRC-5 cells at various doses ranging from 1.25 to 10 mg/ml. Royal jelly's anti-proliferative effect was evaluated by MTT and SRB assay for 48 h. The induction of necrosis and apoptosis was assessed by flow cytometry as well. The relative amounts of major molecules in Royal jelly were determined by FTIR spectroscopy to identify key functional groups and molecular structures. In addition, this technique was used for the first time to detect changes in the macromolecular composition of lung cells treated with royal jelly. Thus, it provided insights into the relative abundance of proteins, lipids, and carbohydrates, which could correlate with their bioactive properties. The antiproliferative effect of Royal jelly was found to be selective on A549 cells in a dose-dependent manner with an IC50 of 9.26 mg/mL, with no cytotoxic effects on normal MRC-5 cells. Moreover, Royal jelly induced predominantly necrotic cell death in A549 cells, %39.10 at 4 mg/ml and %57.88 at 10 mg/ml concentrations. However, the necrosis rate in MRC-5 cells was quite low, at 9.16% and 20.44% at the same doses. Royal jelly showed dose-dependent selective cytotoxicity toward A549 cells, whereas it exhibited no apparent cytotoxicity in MRC-5 cells. In order to identify the biomolecular changes induced by royal jelly, we used two unsupervised chemometric pattern recognition algorithms (PCA and HCA) on the preprocessed sample FTIR spectra to determine the effects of royal jelly on cell biochemistry. According to PCA and HCA results, RJ treatments especially affected biomolecules in A549 cells. The total spectral band variances in the PCA loading spectra were calculated for understanding biomolecular alterations. These plots revealed profound changes in the lipid, protein, and nucleic acid content of RJ-applied lung cells, primarily identifying RJ and H2O2 treated groups for A549 cells. Ultimately, the selective cytotoxicity of royal jelly toward A549 cancerous cells suggests that royal jelly may be a promising therapeutic agent for identifying innovative lung cancer treatment strategies. Additionally, understanding the molecular alterations induced by royal jelly could guide the development of novel cancer treatments that exploit its bioactive properties. This could lead to more effective and safer therapies.

Synthesis of a Gemcitabine Prodrug and its Encapsulation into Polymeric Nanoparticles for Improved Therapeutic Efficacy.

Gemcitabine (GEM), a chemotherapeutic agent, is widely utilized in treating various neoplasm conditions, such as pancreatic, lung, breast, and ovarian cancers. However, its therapeutic effectiveness is often hindered by its hydrophilic nature, short half-life and susceptibility to enzymatic degradation. To address these limitations, in this research, five new prodrugs of GEM were synthesized by conjugating its N-4 amino group with five different acids [4-decenoic acid (4Dec), lipoic acid (Lipo), lauric acid (Laur), 5-benzyl N-(tert-butoxycarbonyl)- L-glutamate (Glu), and decanoic acid (Dec)]. The anticancer potential of these prodrugs was evaluated using CCK-8, annexin-V FITC/propidium iodide staining, ROS, and mitochondrial membrane potential loss assays. Among the conjugates, 4Dec-GEM demonstrated comparable cytotoxic activity to native GEM. To further enhance its therapeutic efficacy, 4Dec-GEM was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles using single-emulsion and high-pressure homogenization, capitalizing on the lipophilicity of the prodrug. The developed nanoparticles were characterized by various techniques and demonstrated successful entrapment of 4Dec-GEM inside PLGA nanoparticles. Finally, the cytotoxicity of developed nanoparticles demonstrated improved therapeutic efficacy as compared to native GEM in A549, MIA-PaCa-2 and PANC-1 cancerous cell lines. Our study demonstrated that the combination of prodrug and nanoparticle can be a promising approach to augment the therapeutic efficacy of GEM.

Alkaloids and Iridoids From Phlogacanthus curviflorus.

Four unreported pyridine alkaloids, curviflorines A-D (1-4), two undescribed iridoids, curviridoids A and B (5 and 6), and one known iridoid glycoside (7), were isolated from the twigs and leaves of Phlogacanthus curviflorus. The structures of these compounds were established by detailed interpretation of MS and NMR data, with the absolute configurations being assigned via comparison of experimental and calculated electronic circular dichroism spectra. Notably, it is the first report of alkaloidal constituents (1-4) from the genus Phlogacanthus. Compounds 1-7 did not show obvious inhibitory activities against α-glucosidase and NO production (in RAW264.7 macrophages), nor did they exhibit anti-oxidant activity and cytotoxicity towards MDA-MB231, A549 and HeLa cancer cell lines. Nevertheless, alkaloids 1-4 did exert a significant suppressing effect on TGF-β1-induced upregulation of the fibrotic marker protein fibronectin in HK-2 cells, indicating their antifibrotic potential.

Selected Metal (Au, Ag, and Cu) Complexes of N-heterocyclic Ligands as Potential Anticancer Agents: A Review.

Nitrogen-based organic heterocyclic compounds are an important source of therapeutic agents. About 75% of drugs approved by the FDA and currently available in the market are N-heterocyclic organic compounds. The N-heterocyclic organic compounds like pyridine, indole, triazoles, triazine, imidazoles, benzimidazoles, quinazolines, pyrazoles, quinolines, pyrimidines, porphyrin, etc. have demonstrated significant biological activities. These heterocyclic organic compounds also coordinate with various metal ions and form coordination compounds. Most of them have shown improved biological activities. The research on the metal complexes of these compounds reported their significant biological activities. N-heterocyclic-based metal complexes showed outstanding anticancer activities against different cancer cell lines, including VEGFR-2, HT-29, MDA-MB-231, MCF-7 K562, A549, HepG2, HL60, A2780, WI-38, Colo-205, PC-3, and other cancer cell lines. Some of these compounds showed better anticancer activity than cisplatin. In this review, we summarized the anticancer properties of N-heterocyclic-based gold (Au), silver (Ag), and copper (Cu) complexes and explored the mechanisms of action and potential structure-activity relationships (SAR) of these complexes. Our goal is to assist researchers in designing highly potent N-heterocyclic-based Au, Ag, and Cu complexes for the potential treatment of various cancers.

Design, synthesis, biological evaluation and multi spectroscopic studies of novel 2-styrylquinoline-carboxamide derivatives as potential DNA intercalating anticancer agents.

In this study, novel 2-styrylquinoline derivatives possessing a planar aromatic system and a flexible side chain with an amino substituent were designed and synthesized as DNA-intercalating antitumor agents. The cytotoxic activity of the synthesized compounds was evaluated against four cancer cell lines including MCF-7 (breast cancer cells), A549 (lung epithelial cancer cells), HCT116 (colon cancer cells) and normal cell line L929 (mouse fibroblast cell line). The results displayed that the anti-cancer activity of the target quinolines is sensitive to the lipophilic nature of the C-6 and C-7 quinoline substituents. The anticancer activity of most of the target quinolines against MCF-7 and A549 cells was more than those of HCT116. Compound 3h possessing two methyl groups at the C-6 and C-7 of quinoline ring displayed the most cytotoxicity with IC50 value of 5.7µM against A549 cancer cells. Interaction of compound 3h with calf thymus DNA (ctDNA) was investigated by means of UV absorption spectrophotometry, fluorescence spectroscopy, circular dichroism (CD), Resonance light scattering (RLS), viscos metric techniques and also by docking and molecular dynamic studies. RLS intensity, fluorescence quenching of ctDNA and fluorescence quenching EtBr-ctDNA and AO-ctDNA complexes augmented with increasing of compound 3h concentration, significant increasing in viscosity and melting point of ctDNA in the presence of compound 3h, absorbance increasing of ctDNA-compound 3h complex by increasing of NaCl and KI concentrations, higher Ksv value for dsctDNA (3.03×104 M-1) compared to ssctDNA (1.31×104 M-1), circular dichroism (CD) studies, docking and molecular dynamic studies revealed that compound 3h can interact with ctDNA through intercalation into DNA.

Biotin functionalization of 8-hydroxyquinoline anticancer organometallics: low in vivo toxicity but potent in vitro activity.

[M(arene)(HQ)Cl] complexes (M = RuII/OsII/RhIII/IrIII; HQ = 8-hydroxyquinoline) have shown promise as anticancer agents. To assess the effect of conjugating biotin (vitamin B7) to such compounds and improve their tumor-targeting ability through interaction with the sodium-dependent multivitamin transporter (SMVT), the chlorido co-ligand was exchanged with biotinylated 6-aminoindazole. The complexes were characterized by NMR spectroscopy and mass spectrometry, and purity was determined by elemental analysis. The compounds were shown to be stable in aqueous solution but reacted in particular with biologically relevant nitrogen-donor ligands. The biotinylated organometallics were shown to be able to interact with the high-affinity biotin-binding protein streptavidin using molecular modelling. High antiproliferative activity of the biotinylated Rh complex (IC50 = 1.1-10 μM) and its chlorido precursor (IC50 = 2.1-7.0 μM) was demonstrated in human HCT116, NCI-H460, COLO 205, SW620, A2780 and A2780cis cancer cells, which feature differing levels of SMVT expression. While there was no clear relationship between the anticancer activity in cells and SMVT expression, the complexes showed similar activity in cisplatin-sensitive and -resistant cells. The most potent was the biotinylated Rh derivative which displayed low toxicity toward zebrafish embryos with >75% survival up to day 4 and after treatment with up to 32 μM complex.

Lauryl-NrTP6 lipopeptide self-assembled nanorods for nuclear-targeted delivery of doxorubicin.

Targeted delivery offers solutions for more efficient therapies with fewer side effects. Here, lipopeptides (LPs) prepared by conjugation of the nuclear-targeting peptide analogue H-YKQSHKKGGKKGSG-NH2 (NrTP6) and two lauric acid chains are used to encapsulate the chemotherapeutic agent doxorubicin (DX) through a solvent-exchange protocol. LPs spontaneously form nanosized rod-like assemblies in phosphate buffer. DX is trapped in the peptide regions of the assemblies. Confocal laser scanning microscopy shows that the peptide assemblies translocate into the nucleus. Cytotoxicity studies over 72 h in A549 and HeLa cancer cell lines show less toxicity for the LP encapsulated DX than for free DX. In contrast, subtoxic doses of encapsulated DX are more effective than free DX in avoiding colony formation over 14 days, with a complete absence of colonies for the LP-encapsulated DX. The results show a more efficient and slow delivery of DX to the nucleus through LP encapsulation, paving the way for the use of lower DX doses as a chemotherapeutic agent.

Triphenylphosphine-modified cyclometalated iridiumIII complexes as mitochondria-targeting anticancer agents with enhanced selectivity.

This study presents the development and evaluation of triphenylphosphine-modified cyclometalated iridiumIII complexes as selective anticancer agents targeting mitochondria. By leveraging the mitochondrial localization capability of the triphenylphosphine group, these complexes displayed promising cytotoxicity in the micromolar range (3.12-7.24μM) against A549 and HeLa cancer cells, these complexes exhibit significantly higher activity compared to their unmodified counterparts lacking the triphenylphosphine moiety. Moreover, they demonstrate improved specificity for cancer cells over normal cells, achieving selectivity index in the range of 5.46-14.83. Mechanistic studies confirmed that these complexes selectively target mitochondria rather than DNA, as shown by confocal microscopy and flow cytometry, where they accumulate to induce mitochondrial dysfunction. This disruption leads to mitochondrial membrane depolarization (MMP), elevated reactive oxygen species (ROS) levels, and activation of intrinsic apoptosis pathways. Furthermore, the complexes induce cell cycle arrest at the G2/M phase and suppress the migration of A549 cells.

Meso-Substituted AB3-type phenothiazinyl porphyrins and their indium and zinc complexes photosensitising properties, cytotoxicity and phototoxicity on ovarian cancer cells.

New meso-substituted AB3-type phenothiazinyl porphyrins and ferrocenylvinyl phenothiazinyl porphyrin were synthesised by Suzuki-Miyaura and Mizoroki-Heck cross-coupling reactions, respectively. The free porphyrins were further used in the synthesis of new indium(iii) or zinc(ii) porphyrin complexes. All porphyrins exhibit red fluorescence emission in solution, a property that remains unimpaired following internalisation in ovarian A2780 cancer cells, as evidenced by fluorescence microscopy images. The In(iii) phenothiazinyl porphyrin complexes show a higher quantum yield of fluorescence emission (2aΦ F = 30%, 4aΦ F = 29%, 5aΦ F = 28%) compared to the free base porphyrin precursors, or Zn(ii) complex 4b (Φ F = 10%). The potential of novel phenothiazinyl porphyrins to act as photosensitisers was evaluated using two distinct approaches. The first was through the measurement of the singlet oxygen quantum yield Φ Δ(1O2), while the second employed in vitro measurements of metabolic activity, oxidative stress, nuclear factor-erythroid 2 related factor 2 (Nrf-2) activation and tumour necrosis factor-alpha (TNF-α) under both dark and light irradiation conditions. As reflected by the IC50 values, the most potent cytotoxicity of the phenothiazinyl porphyrins against the A2780 cells was observed for In(iii) ferrocenylvinyl phenothiazinyl porphyrin 4a (36.38 μM), the remaining compounds are less cytotoxic. The reduction in metabolic activity was observed in A2780 ovarian tumour cells treated with 4a and 6a and exposed to light compared to treatment in the absence of light. The oxidative stress, TNF-α and Nrf-2 transcription factor were particularly notable when A2780 cells were treated with 4a and subsequently photoirradiated, the oxidative stress was linked to the highest value of Φ Δ(1O2) recorded for 4a (60%).

Elucidating the High Affinity Copper(II) Complexation by the Iron Chelator Deferasirox Provides Therapeutic and Toxicity Insight.

Tinoco A-Team Deferasirox (Def), an orally administered iron-chelating drug, has drawn significant interest in repurposing for anticancer application due to the elevated Fe demand by cancer cells. But there are also concerns about its severe off target health effects. Herein Cu(II) binding is studied as a potential off target interaction. The aqueous solution stability and speciation of the ternary complex Cu(Def)(pyridine) was studied by UV-Vis and EPR spectroscopy, ESI-mass spectrometry, and cyclic voltammetry under physiologically relevant conditions. The complex is observed to be a redox active, mononuclear Cu(II) complex in square planar geometry. UV-Vis spectroscopy demonstrates that at pH 7.4 the complex is quite stable (ϵ337nm=10,820 M-1 cm-1) with a log K=16.65±0.1. Cu scavenging from the Cu transporters ceruloplasmin and albumin was also studied. Def does not inhibit ceruloplasmin activity but forms a ternary Cu(II) complex at the bovine serum albumin ATCUN site. Cu(Def)(py) displays potent but nonselective cytotoxicity against A549 cancer and MRC-5 noncancer lung cells but the potency of the ternary protein complex was more moderate. This work elucidates potential Def toxicity from Cu complexation in the body but also cytotoxic synergy between the metal and chelator that informs on new drug design directions.

Dual EGFR and telomerase inhibitory potential of new triazole tethered Schiff bases endowed with apoptosis: design, synthesis, and biological assessments.

Many cancers have displayed resistance to chemotherapeutic drugs over the past few decades. EGFR has emerged as a leading target for cancer therapy via inhibiting tumor angiogenesis. Besides, studies strongly suggest that blocking telomerase activity could be an effective way to control the growth of certain cancer cells. Based on the fact that multi-target design rationale can afford candidates with greater treatment effectiveness. Besides, it was evidenced that inhibition of human telomerase enhances the effect of some tyrosine kinase inhibitors. So, in the current work, we aimed to design and synthesize novel 1,2,3-triazole-tethered Schiff bases (5a-l) to act as dual EGFR and telomerase inhibitors. Growth inhibition (GI)% was conducted for the synthesized compounds using a panel of eleven cancer cell lines as well as two normal cell lines. Interestingly, compound 5e displayed the highest mean GI% (76.78%) among the investigated compounds surpassing the mean GI% of the reference drug doxorubicin (65.79%). In addition, compound 5g displayed notably the lowest IC50 values (13.31, 13.31, 12.62, and 31.19 μM) for the four utilized cancer cell lines HNO97, HCT116, A375, and HEPG2, respectively. Interestingly, the investigated compounds exhibited significant inhibitory potential to EGFR and telomerase protein expression; in particular, compound 5g recorded inhibitory potentials of 3.45 and 1.31 ng mL-1, respectively. Hence, protein expression of the apoptosis-related proteins was carried out for compound 5g. Pro-apoptotic proteins (caspases 3, 8, and 9) were upregulated by 1.35, 1.55, and 1.51-fold change, respectively. Meanwhile, the anti-apoptotic proteins (CDK-2, CDK-4, and CDK-6) were downregulated by 2.91, 2.01, and 9.15-fold change, respectively, ensuring the apoptotic potential of compound 5g. Accordingly, compound 5g was selected for further investigation of its effects on cell cycle progression in A375 cancer cells. Obviously, compound 5g prompted cell cycle arrest at the G0-G1 phase. Additionally, the investigated compounds showed eligible pharmacokinetic profiles with feasible oral bioavailability. Consequently, the synthesized compounds can be treated as lead multi-target anticancer ligands for future optimization.

Triphenylphosphine-Modified IridiumIII, RhodiumIII, and RutheniumII Complexes to Achieve Enhanced Anticancer Selectivity by Targeting Mitochondria.

The incorporation of an organelle-targeting moiety into compounds has proven to be an effective strategy in the development of targeted anticancer drugs. We herein report the synthesis, characterization, and biological evaluation of novel triphenylphosphine-modified half-sandwich iridiumIII, rhodiumIII, and rutheniumII complexes. The primary goal was to enhance anticancer selectivity through mitochondrial targeting. All these triphenylphosphine-modified complexes exhibited promising cytotoxicity in the micromolar range (5.13-23.22) against A549 and HeLa cancer cell lines, surpassing the activity of comparative complexes that lack the triphenylphosphine moiety. Noteworthy is their good selectivity toward cancer cells compared to normal BEAS-2B cells, underscored by selectivity index ranging from 7.3 to >19.5. Mechanistically, these complexes primarily target mitochondria rather than interacting with DNA. The targeting of mitochondria and triggering mitochondrial dysfunction were confirmed using both confocal microscopy and flow cytometry. Their ability to depolarize mitochondrial membrane potential (MMP) and enhance reactive oxygen species (ROS) was observed, thereby leading to intrinsic apoptotic pathways. Moreover, these complexes lead to cell cycle arrest in the G2/M phase and demonstrated antimigration effects, significantly inhibiting the migration of A549 cells in wound-healing assays.

Anticancer and Cyclooxygenase Inhibitory Activity of Benzylidene Derivatives of Fenobam and its Thio Analogues.

A series of benzylidene derivatives of fenobam and its thio analogues (1-22) have been evaluated for their cytotoxicity against breast cancer (MCF-7, MDA-MB-231), ovarian cancer (A2780, SKOV-3) and cervical cancer (HELA) cell lines. These compounds (1-22) exhibited 72-83% inhibition of Erk activity against the ovarian cancer cell line (A2780). Compounds 3 and 20 showed the highest DNA damage effect in Comet Assay against the A2780 cancer cell line as compared to the other tested analogues (4, 8, 11, 12, and 13) by using % Tail DNA and OTM. Compounds 3, 4, and 11 showed significant activities and selectivity towards COX-2 with 78%, 97%, and 89% inhibition, as compared to 17%, 57%, and 26% inhibition against COX-1 isoenzyme, respectively. Interestingly, molecular docking scores were also in very good agreement with the experimental results regarding discriminating the selectivity index of the tested compounds against COX-1 & COX-2 enzymes. Further molecular dynamics (MD) simulation study revealed that the most selective compound, 13, binds with the COX-2 enzyme in a similar fashion to that of Rofecoxib, which was further supported by their MD-based free binding energies (MM-GBSA) of -49.76 ± 4.27 kcal/mol, and -44.84 ±3.78 kcal/mol, respectively. Moreover, in silico ADMET predictions showed adequate properties for these compounds, making them promising leads worthy of further optimization.

Hyaluronic acid-targeted topotecan liposomes improve therapeutic efficacy against lung cancer in animals.

Lung cancer, as a serious threat to human health and life, necessitating urgent treatment and intervention. In this study, we prepared hyaluronic acid (HA)-targeted topotecan liposomes for site-specific delivery to tumor cells. The encapsulation efficiency, stability, chemical structure, and morphology of HA-targeted topotecan liposomes were studied, and the release properties, cellular uptake capacity, and therapeutic efficacy of topotecan were further investigated. Results found that the coupling efficiency of HA on the surface of PEG-coated liposomes was determined to be 13.65 nmol/mg of lipid. The HA-targeted topotecan liposomes demonstrated a high encapsulation efficiency of 95% for topotecan, with an average particle size of 98.26 nm and excellent storage and dispersion stability. Drug release and cellular experiments indicated that the coating of HA further reduced the release rate of topotecan and decreased the survival rate of A549 cells, respectively. Flow cytometry and fluorescence staining analyses revealed that the HA-targeted topotecan liposomes enhanced the uptake of topotecan and exhibited significant anti-tumor effects on A549 cancer cells transplanted in mice. H&E staining showed that the pathological tissue treated with HA-targeted topotecan liposomes corresponded to Miller-Payne grade IV. Furthermore, these liposomes increased the accumulation of topotecan in tumors and extended the blood circulation time of the drug. Therefore, HA-targeted topotecan liposomes can be used as a new and easily prepared carrier in the field of lung chemotherapy, demonstrating considerable potential for anti-tumor therapy.

Synthesis and Characterization of MgO-Fe₂O₃/γ-Al₂O₃ Nanocomposites: Enhanced Photocatalytic Efficiency and Selective Anticancer Properties

In the present work, we achieved the fabrication of MgO-Fe2O3/γ-Al2O3 NCs using a deposition–coprecipitation process. XRD, TEM, and SEM with EDX, XPS, FTIR, and PL spectroscopy were applied to examine the physicochemical properties of the samples. XRD analysis confirmed the successful incorporation of γ-Al2O3, MgO, and Fe2O3 phases. TEM and SEM images indicate that the nanocomposites exhibited an agglomerated morphology with spherical shapes and particle sizes in the range of 6–12 nm. EDX and XPS spectra revealed a composition of MgO-Fe2O3/γ-Al2O3 NCs. FTIR spectra identified characteristic vibrational bands corresponding to the chemical bonds present in the samples, confirming their successful synthesis. PL analysis showed the reduced recombination rate of electron–hole pairs and enhanced charge separation efficiency, which are important factors for improved photocatalytic activity. Photocatalysis results show that the MgO-Fe2O3/γ-Al2O3 NCs exhibited significantly higher photocatalysis efficiencies of 87.5% for Rh B and 90.4% for MB after 140 min, compared to γ-Al2O3 NPs and Fe2O3/γ-Al2O3 NPs. In addition, prepared MgO-Fe2O3/γ-Al2O3 NCs demonstrated superior stability after six runs. Biochemical data showed that the MgO-Fe2O3/γ-Al2O3 NCs exhibited significant toxicity toward A549 cancer cells while displaying low toxicity toward IMR90 normal cells. The IC50 values (µg/mL ± SD) for γ-Al2O3 NPs, Fe2O3/γ-Al2O3 NPs, and MgO-Fe2O3/γ-Al2O3 NCs were 16.54 ± 0.8 µg/mL, 14.75 ± 0.4 µg/mL, and 11.40 ± 0.6 µg/mL, respectively. These results suggest that the addition of Fe2O3 and MgO to γ-Al2O3 not only enhances photocatalytic activity but also improves biocompatibility and anticancer properties. This study highlights that the MgO-Fe2O3/γ-Al2O3 NCs warrant further exploration of their potential applications in environmental remediation and biomedicine.

In Vitro and In Silico Evaluation of Syzygium aromaticum Essential Oil: Effects on Mitochondrial Function and Cytotoxic Potential Against Cancer Cells.

The current study proposes the in vitro and in silico anticancer evaluation of clove (Syzygium aromaticum L.) essential oil (CEO). The steam hydrodistillation method used yielded 10.7% (wt) CEO. GC-MS analysis revealed that the obtained oil is rich in eugenol (75%), β-caryophyllene (20%), and α- caryophyllene (2.8%) and also contains several other minor components accounting for approximately 1.5%. The DPPH-based scavenging antioxidant activity was assessed for the obtained CEO, exhibiting an IC50 value of 158 μg/mL. The cytotoxic effects of CEO, its major component eugenol, and CEO solubilized with Tween-20 and PEG-400 were tested against both noncancerous HaCaT cells and HT-29 human colorectal adenocarcinoma, RPMI-7951 melanoma, A431 skin carcinoma, and NCI-H460 non-small lung cancer cells, using the Alamar Blue and LDH assay after 48 h treatment. The Tween-20 and PEG-400 CEO formulations, at 200 μg/mL, recorded the highest cytotoxic and selective effects against RPMI-7951 (72.75% and 71.56%), HT-29 (71.51% and 45.43%), and A431 cells (61.62% and 59.65%). Furthermore, CEO disrupted mitochondrial function and uncoupled oxidative phosphorylation. This effect was more potent for the CEO against the RPMI-7951 and HT-29 cells, whereas for the other two tested cell lines, a more potent inhibition of mitochondrial function was attributed to eugenol. The present study is the first to specifically investigate the effects of CEO and Tween-20 and PEG-400 CEO formulations on the mitochondrial function of RPMI-7951, HT-29, A431, and NCI-H460 cancer cell lines using high-resolution respirometry, providing novel insights into their impact on mitochondrial respiration and bioenergetics in cancer cells. The results obtained may explain the increased ROS production observed in cancer cell lines treated with eugenol and CEO. Molecular docking identified potential protein targets, related to the CEO anticancer activity, in the form of PI3Kα, where the highest active theoretical inhibitor was calamenene (-7.5 kcal/mol). Docking results also showed that calamenene was the overall most active theoretical inhibitor for all docked proteins and indicated a potential presence of synergistic effects among all CEO constituents.

Cyclodextrins as nanocarriers of hydrophobic silicon phthalocyanine dichloride for the enhancement of photodynamic therapy effect.

In this study, silicon phthalocyanine dichloride (SiCl2Pc) was successfully encapsulated in β-cyclodextrin (β-CD) and hydroxy-propyl-β-cyclodextrin (HP-β-CD) using the kneading method. Dynamic Light Scattering (DLS) demonstrated complexes of various hydrodynamic diameters with moderate stability in aqueous solutions. Their structural characterization by Infrared Spectroscopy (FT- IR) indicated that a part of phthalocyanine is located inside the cyclodextrin cavity. Both photophysical and photochemical studies showed that phthalocyanine's encapsulation in cyclodextrins increased its aqueous solubility. The photodynamic studies against A431 cancer cell line indicated that the complexes are more effective than pure SiCl2Pc. Pure SiCl2Pc's photodynamic effect is characterized as dose-dependent, whereas both complexes presented a biphasic dose-response photodynamic effect. For the highest energy dose of 3.24J/cm2, pure SiCl2Pc induced mild cell toxicity. SiCl2Pc-β-CD complex was the most promising photosensitizer, exhibiting the highest photodynamic effect when irradiated at 2.16J/cm2.