Anticancer Activity Research Articles

Pt(IV) Complexes with Biologically Active and Physicochemical Properties Modifier Ligands

: The octahedral Pt(IV) complexes contain either inert or biologically active ligands where the nature of these axial ligands provides additional stability and synergistic biological activity. There are many literature reports from each of the classes mentioning the varied nature of these axial ligands. The targeting, as well as the non-targeting nature of these moieties, exerts additive or synergistic effects of anticancer activity of Pt(II) moieties. Herein, we have discussed the effects of these axially oriented ligands, changes in the non-leaving am(m)ine groups, and changes in the leaving groups on the biological activity. In this review, we have discussed the axial ligands with a focus on the nature of the ligands and alterations in biological activities.

Multifaceted evaluation of pyrazole derivative (T4)-chitosan (CS) nanoparticles: Morphology, drug release, and anti-tumor efficacy in a rat model.

The development of targeted nanotherapeutics has emerged as a pivotal advancement in cancer treatment, aiming to enhance the efficacy and specificity of drug delivery while minimizing systemic toxicity. Due to their biocompatibility and modifiable surface properties, Chitosan-based nanoparticles have shown considerable promise in encapsulating and delivering therapeutic agents directly to tumor sites. This study investigates the potential of 1,5-diary pyrazole derivative (T4)-loaded chitosan (CS) nanoparticles as a novel anticancer agent, evaluating their physical characteristics, in vivo biodistribution, and therapeutic efficacy against cancerous cells. SEM morphological analysis confirmed chitosan-based nanoparticles' smooth, spherical structure, with aggregation patterns typical of high surface energy nanoparticle synthesis. UV-visible spectroscopy and XRD analysis validated the successful incorporation of T4, showing characteristic absorption peaks and indicating a reduction in crystallinity desirable for enhanced drug release. In vivo imaging demonstrated the rapid systemic distribution of T4-CS nanoparticles, essential for delivering therapeutic agents effectively. The cytotoxic potential of T4-CS nanoparticles was significantly higher against cancer cells compared to controls, confirmed by MTT and scratch assays, indicating enhanced anti-cancer activity and potential inhibition of cancer metastasis. Furthermore, histological and gene expression analyses supported the anti-tumor and pro-apoptotic capabilities of T4-CS nanoparticles, showing reduced proliferation markers and inflammatory pathways. Behavioral assessments in rats highlighted the neuroprotective effects of T4-CS nanoparticles against 7,12-dimethyl benzanthracene (DMBA) induced neurotoxicity, suggesting their utility as both anticancer and neuroprotective agents. This multifaceted evaluation underscores the versatility and therapeutic potential of T4-CS nanoparticles, warranting further investigation into their mechanistic effects and clinical applications.

Exploring the Effect of Gomisin A on Non-Small Cell Lung Cancer With Network Pharmacology, Molecular Docking, InVitro and InVivo Assays.

Gomisin A is an active ingredient of Schisandra chinensis. Pre-clinical studies suggest Gomisin A has good anti-cancer activities against a variety of cancers, but its mechanism of action in non-small cell lung cancer (NSCLC) is unclear. This study aims to explore the potential mechanism of Gomisin A in treating NSCLC. The SwissTargetPrediction, CTD, HERB and PharmMapper databases were used to collect related targets of Gomisin A. NSCLC-related genes were obtained using the GEO, CTD, DisGeNET, OMIM, GeneCards, NCBI, and PharmGKB databases. The central targets and potential mechanisms of Gomisin A against NSCLC were screened using network pharmacology and molecular docking. Finally, the therapeutic activity of Gomisin A on NSCLC was verified by experiments. A total of 161 potential targets of Gomisin A against NSCLC were identified. TNF, AKT1, STAT3, and IL6 were identified as the central targets of Gomisin A. The binding energy of Gomisin A and the central targets was less than -5 kcal/mol. Gomisin A could inhibit NSCLC cell viability, migration and invasion and induce cell cycle arrest and apoptosis. Gomisin A also inhibited invivo metastasis of NSCLC cells. In addition, Gomisin A could also reduce the expression level of the central targets and inhibit the PI3K-Akt signaling pathway. In summary, Gomisin A may be a candidate drug for the treatment of NSCLC, and TNF, AKT1, STAT3, and IL6 are potential targets for Gomisin A in NSCLC treatment, and its therapeutic mechanism may be related to the PI3K-Akt signaling pathway.

Non-nucleophilic base promoted synthesis of azo-linked oxazolone-pyrazole hybrids: Antimicrobial, antitubercular, anticancer evaluations and in-silico modeling insights

Ten new non-nucleophilic base (DBU) catalyzed oxazolone-bearing pyrazole derivatives were created to treat infectious diseases caused by bacterial, mycobacterial strains, and cancerous cell lines. Compounds 7b and 7c showed excellent antibacterial and antifungal activity. Compound 7b was highly effective against M. tuberculosis H37Rv, with a MIC of 0.06 μg/mL and significant binding affinities to AcrB of E. coli (−12 Kcal/mol), TriABC of P. aeruginosa (−12.5 Kcal/mol), and MepR of S. aureus (−10.6 Kcal/mol). Based on the findings, compounds 7b, 7c, and 7e exhibit proficient binding affinity with two essential targets, namely Enoyl-[acyl-carrier-protein] reductase and Topoisomerase I, of M. tuberculosis. Compound 7b showed superior cytotoxic activity against all cancer types except leukemia with GI50 values of 1.26–1.83 µM and LC50 values of 5.36–7.88 µM. Compound 7a demonstrated remarkable anticancer activity against colon, melanoma, ovarian, renal, and breast cancer cell lines with GI50 values of 1.60–2.55 µM.

Differential Effects of Punicic Acid on Cytotoxicity and Peroxiredoxin Expression in MCF-7 Breast Cancer and MCF-10A Normal Cells.

The pomegranate fruit has been associated with a variety of human health benefits based on its antioxidant and anti-inflammatory properties. Punicic acid (PA) is an omega-5 long chain polyunsaturated fatty acid that constitutes approximately 65-80% of the oil from pomegranate seeds and has been found to possesses anti-cancer activity in various cancer types. To better understand its cell specificity, we investigated the effects of punicic acid on both the MCF-7 human breast cancer cell line as well as the non-cancerous MCF-10A breast epithelial line. We treated both cell types with different concentrations of punicic acid and measured viable cell density, cytotoxicity and apoptosis, as well as peroxiredoxin (Prdx) antioxidant expression. We found that punicic acid was cytotoxic to both lines, but MCF-10A cells demonstrated higher levels of cytotoxicity and sensitivity to lower concentrations. We further demonstrated that cytotoxicity was associated with apoptosis in both lines. Using real time PCR, we demonstrated induction of all six Prdx mRNAs in MCF-7 cells, ranging from a 1.4-fold increase with 2 μg/ml, to over a 5-fold increase with 10 μg/ml. In stark contrast, MCF-10A cells exhibited considerably higher induction of all six Prdx mRNAs at 10μg/ml, exceeding a 30-fold induction of Prdx1, Prdx2 and Prdx5. Our data are the first to demonstrate differential cytotoxicity and Prdx regulation by punicic acid in these two cell lines. These results may provide important insight into cell-specific mechanisms of punicic acid in breast cancer.

Environment-friendly Synthesis of AgNPs from Fimbristylis miliacea Flower Extract: Characterization and its Applications as an Antioxidant Activity, Anticancerous Activity and in the Reduction of 4-Nitrophenol

Background: Silver metal is useful in a variety of fields. Different silver salts exhibit good application in the organic transformation. The use of a green methodology in AgNPs preparation has gained interest of young researchers. Plant systems are employed in the green approach of preparing AgNPs, serving as both a stabilizing and reducing agent. Silver nanoparticles (AgNPs) made from silver salts exhibit a variety of biological activities and may be useful in organic transformation. Method: AgNPs were synthesized with the use of flower extract from Fimbristylis miliacea, which acts as a stabilizing and reducing agent. Result: Fimbristylis miliacea flower extract is used as a reducing and stabilising agent for preparation of AgNPs. These synthesised AgNPs were characterised by using FTIR, XRD, FESEM/ EDS, HR-TEM, TGA, and ICP-AES. Fimbristylis milliciea flower extract was subjected to FTIR and HR-LCMS analysis in order to identify the phytoconstituents that are responsible for the reduction of AgNO3. The HR-TEM shows particle size between 8.98434+0.69669nm and 19.07464+1.4384nm. The size of AgNPs determined by using HR-TEM shows good agreement with XRD particle size. The synthesized AgNPs show excellent antioxidant properties with IC50=56.45 μg/mL. The present study confers significant cytotoxic activity against MDA-MB-231 human breast cancer cell line culture (IC50= 61.97 μg/ml). The AgNPs show a faster reduction of 4-nitrophenol. Conclusion: In conclusion, we have prepared AgNPs by using Fimbristylis miliacea flower extract. The study further concludes that green synthesis of AgNPs has many advantages as compared to chemical methods, such as cost-effectiveness, rapid, and environment-friendly methods. The results indicated that the biosynthesized AgNPs have significant cytotoxic activity against the MDA-MB-231 breast cancer cell line. Further, it indicates that biosynthesized AgNPs can be a potential alternative agent for human breast cancer therapy. The cytotoxic potential can be used for treatments and provides a new method to develop molecules for cancer therapy. The catalytic activity of AgNPs was examined by using the reduction of 4-nitrophenol. It shows that the reduction of 4-nitrophenol in 6 minutes is confirmed by using 1H NMR 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.

Evaluation of Antioxidant and Breast Cancer Cytotoxicity of Beta vulgaris and Daucus carota Methanol Extracts

Breast cancer is the world's most frequent malignancy among women. Many dietary antioxidants have been shown to help prevent oxidative stress, which has been linked to a variety of diseases, including cancer. Many chronic diseases, such as cancer, can be avoided by eating fruits and vegetables on a regular and balanced basis. The current study's goal is to assess the antioxidant and cytotoxic capabilities of methanolic extracts of Beta vulgaris and Daucus carota against MCF-7 human breast cancer cell lines. Therefore, the aim of the present study was to determine the phytochemical components, antioxidant capacity, total phenolic & flavonoid contents in the methanolic extracts of Beta vulgaris and Daucus carota. Further, MTT assay against breast cancer cell line (MCF-7) was performed for the evaluation of cytotoxic activity. The majority of secondary metabolites were found in both the aqueous and methanolic extracts of Beta vulgaris and Daucus carota. Beta vulgaris and Daucus carota have different total phenolic and flavonoid contents. TLC results showed many spots having different Rf values. Moreover, we observe comparable cytotoxic activity in both the extracts against MCF-7 cell lines. Our results reveal that the methanolic extracts of Beta vulgaris and Daucus carota has effective phytochemical constituents, antioxidant and anticancer activity. The total phenolic and flavonoid contents vary between Beta vulgaris and Daucus carota. Further studies are needed to evaluate the chemopreventive potentials of the Beta vulgaris and Daucus carota extract when used alone or in combination with doxorubicin to mitigate the toxic side-effects of the latter.

Methanolic Extract of the Nutritional Plant (Diospyros kaki Thunb.) Exhibits Anticancer Activity by Inducing Mitochondrial Dysfunction in Colorectal Cancer Cells.

Background/Objectives:Diospyros kaki, the most widely cultivated species of persimmon, has been long used in traditional medicine since its leaves' extracts contain high amounts of flavonoids and terpenoids, endowed with several beneficial effects. However, its anticancer activity towards colorectal cancer (CRC) has not been investigated in depth. Methods: The effect of a methanolic extract of D. kaki leaves, rich in kaempferol and quercetin derivatives, have been evaluated on an E705 CRC cell line, representative of most CRC patients, and on SW480 cells, carrying a KRAS-activating mutation. Results: This extract is effective in reducing tumor cells' viability without affecting the healthy mucosa cell line CCD 841. In fact, Western blot experiments showed its ability to induce apoptosis in cancer cells by increasing oxidative stress and disrupting mitochondrial functionality, as shown by reactive oxygen species measurement and Seahorse analysis. Conclusions: With the aim of increasing healthspan, as well as the substantial societal and macroeconomic costs associated with cancer, our results could pave the way to a role for D. kaki extract in both CRC treatment and prevention.

Activities of Chalcone Derivatives from Boesenbergia rotunda Against Human Estrogen Receptor Alpha of Breast Cancer by In Silico

The high prevalence of cancer must be overcome with prompt and appropriate prevention and treatment. New drug design is an effort to develop existing drugs, and their molecular structure and biological activity have been known through structural modification. It encourages researchers to explore Indonesia's natural resources, especially plants with anticancer activity, namely by synthesizing chalcone-derived compounds derived from the isolation of Fingerroot rhizomes (Boesenbergia rotunda). The most common flavonoid compound found in rhizomes fingerroot plants is pinostrobin. Pinostrobin compounds and their derivatives are synthesized, resulting in chalcone compounds and their derivative modifications. The author conducted an in-silico test on pinostrobin compounds and 19 of their derivatives, chalcone compounds, and 18 derivatives using estrogenic-a receptors with PDB codes 3ERD and 1G50. The author hoped that from this silico test, compounds with more potential as anticancer for breast cancer would be obtained based on the results of docking with 3ERD and 1G50 receptors and can then be synthesized. In the results of this study, the compounds Bis-4-bromobenzyoxychalcone and Bis-4-chlorobenzyloxychalcone are the most appropriate compounds to be synthesized. It is hoped that in the future, they can be continued with activity tests of these compounds, both in vitro and in vivo, because these compounds are predicted to have the best activity and do not have hepatotoxic or other toxicity effects

Influence of Composition and Structure of Charge Transfer Complexes of Tioconazole on Their Spectral Properties and Anticancer Activity

Influence of Composition and Structure of Charge Transfer Complexes of Tioconazole on Their Spectral Properties and Anticancer Activity

A lncRNA Transcriptome Analysis of Phycocyanin-Treated Non-Small Cell Lung Cancer A549 Cell Lines

Phycocyanin is a type of marine food additive with multiple biological properties, including anticancer activity, but its underlying antineoplastic mechanism in non-small cell lung cancer (NSCLC) remains unclear. To investigate the underlying regulatory mechanism of phycocyanin in NSCLC, a lncRNA microarray analysis was performed using a phycocyanin-treated A549 cell model. The classification and expression of lncRNAs were determined. The profiles of differentially expressed lncRNAs were generated and analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The results showed that 193 lncRNAs were upregulated and 116 lncRNAs were downregulated in the phycocyanin-treated group compared with the control group, and qRT‒PCR analysis confirmed the expression of selected lncRNAs. Bioinformatic analysis indicated that the differentially expressed lncRNAs and their target genes were enriched in the extracellular region, epithelium development, NOD-like receptor pathway, Notch signaling, and apoptosis process. In addition, coexpression network analysis identified 2,238 lncRNA‒mRNA, lncRNA‒lncRNA, and mRNA‒mRNA pairs. In particular, 72 etc. differentially expressed lncRNA target genes were discovered in the interaction network, which provides insights into the potential mechanism of phycocyanin in A549 cells. Moreover, cell phenotype experiments showed that downregulating the expression of lncRNA ENST00000538717, a lncRNA that is downregulated after phycocyanin treatment, could significantly inhibit the migration and viability of A549 and H460 cells. In conclusion, this study lays a theoretical and potential foundation for NSCLC treatment and advances our understanding of the regulatory mechanisms of phycocyanin.

Molecular docking and ADME evaluation of plant-based bioactive molecules targeting nonsense-mediated mRNA decay pathway factors to modulate tumorigenesis

Cancer is a global health challenge that requires continuous efforts to discover effective anticancer drugs. Phytochemicals are compounds found in plants that often have medicinal properties. They possess a wide range of bioactive properties, including anticancer activity. Their multiple mechanisms of action in different physiological processes in humans make them promising candidates in the anticancer therapeutics development. The presence of these compounds makes plants valuable resources for traditional medicine and modern pharmaceutical research as well. Natural products from plants and marine sources are being used to find new anticancer agents. In humans, different cellular pathways are involved in the tumorigenesis process. Many studies have shown the role of the nonsense-mediated mRNA decay (NMD) pathway in the process of tumorigenesis. This NMD pathway is controlled by multiple proteins. In this study, we conducted a molecular docking analysis of 50 phytochemicals against the human NMD factor up-frameshit2 (UPF2) protein. The results of the molecular docking experiment and ADME properties indicate that 4 of these molecules (Genistein, Trihydroxyflavone, Baicalein and Epigallocatechin) have the potential to modulate the NMD pathway. Furthermore, these molecules comply with Lipinski's rule of five. The effects of these 4 phytochemicals may be further evaluated using in vitro and in vivo methods for novel anticancer therapeutic development.

Fatty acid composition and anti-cancer activity of essential oil from Tenebrio molitor larvae in combination with zoledronic acid on prostate cancer

The essential oil extracted from Tenebrio molitor larvae (EOTM) is a natural product containing trace elements with potential therapeutic properties. This study aimed to assess the anticancer effects of EOTM and its synergistic interactions with zoledronic acid, a bisphosphonate drug, on prostate cancer cell lines. The chemical composition of EOTM was analyzed using GC-MS revealing a high concentration of fatty acids. The cytotoxicity of EOTM, both as a standalone treatment and in combination with zoledronic acid, was evaluated on prostate cancer cell lines (LNCaP, PC3) and normal hSKM using MTT assays. Results demonstrated that EOTM exhibited selective toxicity, inhibiting the growth of cancer cells in a dose-dependent manner while sparing normal cells. Morphological assessments and gene expression analyses of BCL2 and BAX were conducted through microscopy, Western blotting, and real-time RT-qPCR. These analyses indicated that EOTM induced apoptosis in cancer cells, as evidenced by cellular shrinkage, membrane blebbing, and nuclear fragmentation. Western blot results showed that EOTM downregulated the anti-apoptotic protein BCL2 and upregulated the proapoptotic protein BAX, suggesting activation of apoptosis pathways. Additionally, the combination of EOTM with zoledronic acid amplified these effects. Hoechst 33258 staining further confirmed the purity of cells following treatment. In conclusion, EOTM exhibits strong anticancer properties by inducing apoptosis in prostate cancer cells and demonstrates synergistic potential when combined with zoledronic acid. These findings warrant further investigation of EOTM as a natural and effective cancer treatment option.

Virtual screening and lead optimization of Desmostachya bipinnata-derived FGFR inhibitors for oral squamous cell carcinoma management

BackgroundOral cancer remains a major global health challenge with limited therapeutic options, highlighting the need for novel treatments. Phytochemicals derived from Desmostachya bipinnata (Db), a plant used in traditional Chinese medicine for its anti-inflammatory and analgesic properties, have demonstrated potential anti-cancer effects. However, their mechanisms of action, particularly in targeting Fibroblast Growth Factor Receptor (FGFR) in oral cancer, are not well characterized. ObjectiveThis study aimed to leverage in-silico drug design methodologies to identify bioactive compounds from Db with potential FGFR-inhibiting activity for the treatment of oral cancer. MethodologyAn MTT assay was conducted using KB cell lines to evaluate cytotoxic effects, while thirty-eight phytochemicals from Db were screened through in silico approaches for their pharmacokinetics, toxicity, and drug-likeness. Molecular docking studies were performed to assess binding affinities to the FGFR protein. The biological activity and toxicity of the compounds were predicted to prioritize candidates for further investigation. ResultsFourteen compounds were identified as promising candidates based on their drug-like properties, favourable pharmacokinetic profiles, significant FGFR binding affinities, and predicted anti-cancer activity. These compounds also demonstrated potential for oral bioavailability and central nervous system penetration, supporting their candidacy for further drug development. Notably, the traditional use of Desmostachya bipinnata in TCM emphasizes its role in enhancing overall vitality and immune function, which may synergize with the identified FGFR-inhibiting properties in the context of oral cancer treatment ConclusionThe phytochemicals from Desmostachya bipinnata exhibit significant potential as FGFR-targeted therapeutic agents for oral cancer. Further experimental validation and optimization of these lead compounds could contribute to the development of novel, effective treatments for oral cancer and related conditions

Fabrication of curcumin-loaded nano-micelles based on quercetin-quarternary ammonium-chitosan (Qu-QCS) conjugate and evaluation of synergistic effect with doxorubicin against breast cancer

The applications of quarternized chitosans have achieved notable success in the development of drug-delivery systems. This study reported the preparation of quercetin-quarternized chitosan (Qu-QCS) conjugate and its application for the fabrication of stable and safe curcumin (cur) loaded nano-micelles with high targeting ability and selectivity towards the breast cancer cell lines. Moreover, doxorubicin (dox) was co-treated with the nanomicelles to enhance the efficacy and reduce the cardiotoxic effects of dox. Structural properties of Qu-QCS were evaluated by FTIR, DSC, and XRD analysis and the yield obtained was 48.82 %. The nano-micelles obtained showed spherical shape, <200 nm size, 48.38 % entrapment efficiency, prolonged stability at 4 °C and pH-responsive release pattern. The cur-loaded nano-micelles showed higher activity and selectivity against breast cancer (MCF-7 and MDA-MB-231) cell lines with enhanced internalization, lower toxicity to the normal cardiomyoctyes (H9C2), enhanced the cell cycle arrest at the G2/M phase of the breast cancer cell lines and induced apoptosis with high intensity compared to pure cur. Moreover, the co-treatment of dox with cur-loaded Qu-QCS nano-micelles showed increased anticancer activity and reduced cardiotoxicity. Overall, this study suggests the potential applications of cur-loaded Qu-QCS micelles in the delivery of chemotherapeutic agents and complementary support in combination with chemotherapeutic agents.

Synthesis, Structure, and In Vitro Biological Evaluation of Semi-Synthetic Derivatives of Betulin

Betulin and α-lipoic acid are naturally occurring substances with different biological properties. Combining two phytochemical units into a conjugate is a frequently used method to obtain new compounds with better pharmacokinetic parameters. This research concerned the preparation of lipoate derivatives of betulin using the Steglich method. Experimental lipophilicity values were determined for target compounds 6–10 by reversed-phase thin-layer chromatography. In silico methods were used to calculate the physicochemical parameters and lipophilicity of new derivatives and to determine the probable directions of biological activity. α-Lipoic acid, betulin, and lipoate derivatives 6–10 were tested for antiproliferative activity against MV4-11, A549, MCF-7, PC-3, HCT116, MiaPaca-2, and Hs294T cancer cells. 3-(5-(1,2-Dithiolan-3-yl)pentanoyl))betulin 10 showed moderate anticancer activity against MV4-11, PC-3, and HCT116, with IC50 values in the range of 39.8–76.7 µM. The introduction of a dithiolate substituent at the C3 position in 28-acetylbetulin gave compound 9 the highest activity (IC50 = 37.9 µM), in the ratio of biphenotypic B myelomonocytic leukemia cells (MV4-11). All lipoate derivatives were inactive towards normal cells.

Human decidua basalis mesenchymal stem/stromal cells enhance anticancer properties of human natural killer cells, in vitro.

Mesenchymal stem cells/stromal cells from the Decidua Basalis of the human placenta (DBMSCs) express wide range of effector molecules that modulate the functions of their target cells. These properties make them potential candidate for use in cellular therapy. In this study, we have investigated the consequences of interaction between DBMSCs and natural killer (NK) cells for both cell types. DBMSCs were cultured with IL-2-activated and resting non-activated NK cells isolated from healthy human peripheral blood and various functional assays were performed including, NK cell proliferation and cytolytic activities. Flow cytometry and microscopic studies were performed to examine the expression of NK cell receptors that mediate these cytolytic activities against DBMSCs. Moreover, the mechanism underlying these effects was also investigated. Our findings revealed that, co-culture of DBMSCs and NK cells resulted in inhibition of proliferation of resting NK cells, while proliferation of IL-2 activated NK cells was increased. Contrarily, treatment of DBMSC's with comparatively high numbers of IL-2 activated NK cells, resulted in their lysis, whereas treatment with low numbers resulted in reduction in their proliferation. Cytolytic activity of NK cells against DBMSCs was mediated by several activating NK cell receptors. In spite of the expression of HLA class I molecules by DBMSCs, they were still lysed by NK cells, excluding their involvement in cytolytic activity. In addition, preconditioning NK cells by DBMSCs, enhanced their ability to suppress tumor cell proliferation and in severe cases resulted in their partial lysis. Lysis and decrease of tumor cell proliferation is associated with increased expression of important molecules involved in anticancer activities. We conclude that DBMSCs exhibit dualfunctions on NK cells that enhance their anticancer therapeutic potential.

Synthesis, Characterization, in Silico and in vitro Screening of Anticancer Activity of Novel Curcumin Analogues

Global problem of cancer associated side effects with current chemotherapeutics and promising anticancer activity of curcumins, intended present study to carry out the synthesis of some new curcumin analogues using chromone aldehydes and cyclic ketones. The study involved in silico screening and in vitro anticancer evaluation of new synthesized compounds against the breast cancer cell line MDA-MB-231 using the MTT assay. All synthesized compounds exhibited significant cytotoxicity, with IC50 values ranging from 34.04 ± 0.05 µg to 43.96 ± 0.05 µg, comparable to the standard drug cisplatin (IC50 = 29.25 ± 0.14 µg). Among all new synthesized curcumin analogues, compound 2 exhibited the highest anticancer activity. Molecular docking studies supported these findings, demonstrating strong binding affinities of the chromone compounds to key protein targets EGFR (PDB ID: 3UG2) and ERBB2 (PDB ID: 3H3B), critical in breast cancer pathogenesis. The strong cytotoxic effects and binding affinities suggest that curcumin analogues could serve as promising candidates for developing targeted anticancer therapies.

Gold(I) complexes of the type [AuL{κC-2-C6H4P(S)Ph2}] [L = PTA, PPh3, PPh2(C6H4-3-SO3Na) and PPh2(2-py)]: Synthesis, characterisation, crystal structures, and In Vitro and In Vivo anticancer properties

Four new mononuclear gold (I) compounds of the type [AuL{κC-2-C6H4P(S)Ph2}] {L = PTA (1), PPh3 (2), PPh2(C6H4-3-SO3Na) (3), and PPh2(2-py) (4)} were prepared by scission of the dinuclear compound [Au2{μ-2-C6H4P(S)Ph2}2] by L or via a transmetalation reaction using the organotin reagent 2-Me3SnC6H4P(S)Ph2 and a suitable gold halide precursor. The cytotoxic potential of complexes 1–4 was evaluated against four human cancer cell lines of diverse cellular origin: cervical (HeLa), prostate (PC-3), non-small cell lung adenocarcinoma (A549), and fibrosarcoma (HT-1080). The in vitro cytotoxicity results showed that 1 demonstrated exceptional anticancer activity with IC50 values ranging from 0.08 to 3.5 μM. Complex 3, which contains a sulfonated triphenyl phosphine ligand, displayed the weakest anticancer activity with IC50 values ranging from 3.1 to >50 μM. When compared to the standard chemotherapeutic drug cisplatin, 1 displayed approximately 27-fold greater cytotoxic activity against cervical cancer cells and 3.5- and 7.5-fold greater activities against prostate and fibrosarcoma cancer cells, respectively. Additionally, 1 exhibited 3-fold selectivity for cervical cancer cells compared to non-cancerous HEK-293 cells. Mechanistic investigations revealed that 1 induced apoptosis, which was associated with elevated reactive oxygen species (ROS) and inhibition of the intracellular enzyme thioredoxin reductase. Furthermore, 1 exhibited notable antiangiogenic characteristics in an in vivo model using transgenic zebrafish Tg(fli1a:EGFP). In vivo studies using mouse xenograft models showed that complex 1 displayed superior inhibition of tumour growth (82 %) compared to the clinical drug cisplatin (29 %). Overall, these results highlight the potential of gold (I) compounds as novel antitumour agents.