Leukemia Cancer Cells Research Articles

New Ru(III) 2,6-Bis(2-benzimidazolyl)Pyridine Complexes Bearing p-sub-Benzyl Thiosemicarbazones Schiff Base: Synthesis, Characterization, DNA Binding and Anti-cancer Activity.

The six mononuclear Schiff's base Ru(III) complexes viz., [Ru(BZP)(LA)2].2NO3 (MRA), [Ru(BZP)(LB)2].2NO3 (MRB), [Ru(BZP))(LC)2].2NO3 (MRC), [Ru(BZP))(LD)2].2NO3 (MRD), [Ru(BZP)(LE)2].2NO3 (MRE) and [Ru(BZP)(LF)2].2NO3 (MRF), [(BZP = 2,6-bis(2-benzimidazolyl)pyridin], were synthesized using of p-sub-benzylthiosemicarbazones (BTS) [(Sub = 4-NO2 (LA), 4-N(CH3)2 (LB), 4-Cl (LC), 4-OCH3 (LD), 4-OCH2Ph (LE), 4-OH (LE)] and 4-OH (LF), as an ancillary ligand. The thiosemicarbazones ligands (LA-LF) were obtained by the condensation of p-substituted benzaldehyde and thiosemicarbazide. These complexes were characterized by elemental analysis, IR, ESR, ESI-MS, electronic absorption spectroscopy. The geometry was optimized by theoretical calculation using DFT and structure reveals that MRA-MRF adopt octahedral geometry. Further, the complexes were examined for anticancer against Leukemia cancer cell line K562 and shown significant responses to these cells. Moreover, DNA binding studies were studied with all complexes MRA-MRF and the binding constant (Kb) were found 1.54 x 104, 2.87 x 104, 1.67 x 104, 1.98 x 104 and 1.59 x 104, respectively. It was found that DNA binds in intercalation mode which is also validate by the Docking studies.

Platinum(ii) complexes of aryl guanidine-like derivatives as potential anticancer agents: between coordination and cyclometallation.

The preparation of a wide variety of Pt(ii) complexes with aryl guanidines and their potential application as anticancer agents have been explored. A relatively facile synthesis of cyclometallated Pt(ii) complexes of arylguanidines, preparation of Pt(ii) guanidine coordination complexes and an in situ activation of platinum arylguanidine complexes with acetonitrile to create a bidentate aryl iminoguanidine Pt(ii) complex were achieved. Cyclometallation methodology was extended to create a water-stable conjugate incorporating two Pt(ii) ions and a diaryl bis-guanidine DNA minor groove binder. Several crystal structures were obtained confirming these complexation modes. The cyclometallated Pt(ii) complexes were particularly stable to aqueous environments and were tested for Reactive Oxygen Species generation and anticancer activity in a leukaemia cancer cell line.

Biological evaluation of newly synthesized α-benzyl monoxime thiocarbohydrazide derivatives as an antimicrobial and anticancer agent: In vitro screening and ADMET predictions.

The current comprehensive study showcases a meticulous synthesis of novel class of α-benzilmonoxime thiocarbohydrazide (BMOTC) derivatives, and manifesting their multifaceted potential as antibacterial, antifungal, and anticancer agents. The synthesis of target compounds was performed in three phases using literature methods. In the first step, benzilmonoxime is synthesized using benzil and hydroxyl amine hydrochloride, followed by benzilmonoxime imine using thiocarbohydrazide. The final stage involves combining BMOTC imine with various aldehydes and ketones. The antibacterial and antifungal activities of the synthesized derivatives against five bacterial panels, both Gram-positive and Gram-negative, and one fungal pathogen have been screened. Twelve of the twenty-four synthetic derivatives showed noteworthy activity; eight derivatives exhibited growth inhibition (GI) >73 % against Acinetobacter baumannii, two exhibited GI >95 % against Escherichia coli, and two exhibited GI >93 % against Candida albicans at concentration 32 μg/mL. Further assessment revealed that two derivatives 5v and 5w, exhibited negligible cytotoxicity towards human embryonic kidney cells (HK-293) and human red blood cells (RBC), signifying their promising safety profile at concentration 32 μg/mL (GI against Candida albicans - 97.51 % and 93.71 % respectively). The synthesized compounds were subjected to in vitro cytostatic activity, where a rigorous scrutiny against a diverse panel of NCI 60 cancer cell lines representing various malignancies was carried out. A total of eleven compounds emerged as promising candidates, demonstrating significant growth percent (GP) at a concentration of 10 µM. Notably, compounds 5d, 5h, and 5x, turned up as standout performers, exhibiting potent anticancer activity across multiple cancer types, including colon, CNS, melanoma, and breast cancers. Of particular interest, compound 5d displayed notable antiproliferative effects against leukemia cancer cell lines RPMI-8226 & SR, while maintaining non-cytotoxicity against the same. Compound 5h showcased activity against ovarian, non-small cell lung, and prostate cancers, without inducing cytotoxic effects. Compound 5x demonstrated remarkable anticancer activity against leukemia and breast cancer cell lines, further bolstered by its non-cytotoxic nature. A compelling aspect of this study is the comparative analysis with the established drug molecule sunitinib, revealing that compounds 5d, 5h, and 5x exhibit superior potency. These findings not only highlight the therapeutic potential of the BMOTC derivatives but also underscore their viability as promising candidates for future drug development endeavours. This study serves as a pivotal step towards harnessing the untapped therapeutic potential of BMOTC derivatives in combating microbial infections and advancing cancer therapy.

Antiproliferative Effect of Spilanthes Acmella Extracts on Human Cervix Adenocarcinoma and Human Myelogenous Leukemia Cells

Abstract Reactive oxygen and nitrogen species (RONS) play a crucial role in the pathogenesis of various chronic diseases, including cancer, by reacting with fundamental biomolecules. While conventional anticancer treatments such as ionizing radiation and chemotherapy have significant adverse effects, some medicinal plants exhibit free radical scavenging and anticancer activities. Spilanthes acmella L., commonly known as the toothache plant, is reported to have various bioactive compounds with antioxidant and anticancer properties. The aim of this study was to investigate and evaluate antiproliferative potential of Spilanthes acmella ethanolic extract on human cervix adenocarcinoma (HeLa) and human myelogenous leukemia (K562) cancer cell lines. The stock solution of Spilanthes acmella extract was prepared in ethanol at concentration of 1 mg/mL and diluted with complete nutrient medium RPMI-1640. The medium was supplemented with 3 mM l-glutamine, 100 μg/mL streptomycin, 100 IU/mL penicillin, 10% heat-inactivated fetal bovine serum (FBS), and 25 mM Hepes, adjusted to pH 7.2. Cell survival was determined by the MTT assay 72 hours post-treatment. The IC50 values were calculated using a dose-response growth curve. The S. acmella ethanolic extract demonstrated significant cytotoxic (antiproliferative) effects on both HeLa and K562 cancer cell lines. The extract exhibited higher cytotoxicity towards K562 cells, with an IC50 value of 29.1 µg/mL, compared to HeLa cells, which had an IC50 value of 48.8 µg/mL. Spilanthes acmella extract possesses considerable potential as an anticancer agent and warrants further in vivo investigations to confirm its efficacy.

Highly Efficient and One-pot New Betti Bases: PEG-400 and Al2O3 Mediated Synthesis, Optimizations, and Cytotoxic Studies

Background: Multicomponent reactions (MCRs) have proven as one of the best alternatives to minimize several environmental consequences, mainly the use of hazardous chemicals, byproducts, and severe production processes. Literature reveals that MCRs with PEG-400 and metal oxide-based greener media provide a new and useful strategy for the construction of biologically potent organic systems. Objective: The present study aimed to synthesize newer Betti bases by a modified Betti reaction employing a highly efficient catalyst for the direct synthesis of a novel class of non-racemic amino benzyl naphthol ligands under green solvent media. The involvement of the articulated framework (4a-4j) was studied against nine cancer panels (NCI-60 cell lines) in terms of inhibiting/killing cancer cells. Methods: For the modification of the Betti reaction, we used 2-aminopyridin-3-ol, aromatic aldehydes, and a naphthol system using greener media employing PEG-400 and alumina as a prime active and highly selective catalyst. Furthermore, the antiproliferative activity against NCI-60 human cancer cell lines (GI50) was used for the development of pharmacologically active compounds and exhibited the single dose (10-5 M) study. Results: Based on greener media synthesis, recompenses of ease of workup, less reaction time, higher yield, and higher atom economy, as well as environmentally friendly, were reported. Betti bases were obtained at a yield of 87-98% and characterized by spectroscopic techniques. Among the synthesized scaffolds, compound 4b was found to be extra potent in melanoma cancer [MDAMB- 435], while compound 4h showed promising inhibition in leukemic cancer cell lines [HL- 60(TB) and MOLT-4]. Conclusion: A straightforward way for an efficient synthesis of Betti bases was developed via the reaction of naphthol and aldehydes with amines in PEG-400 media. An Al2O3 was effectively catalyzed in the Betti reaction in excellent yields without the formation of any other by-product in atom economy and environmentally benign way. The newly synthesized hybrids were tested in vitro against a panel of cancer cell lines, and some of the compounds exhibited significant inhibitory anti-proliferative effects. The most potent compounds (4b and 4h) showed interesting results, and compound 4b was found extra potent in melanoma cancer cell lines with -62% GI values.

Discovery of the Aminated Quinoxalines as Potential Active Molecules

Background: In recent years, as the biological activity of the quinoxaline skeleton has been revealed in numerous studies, interest in synthesizing new prototype molecules for the treatment of many chronic diseases, especially cancer, has increased. Methods: The desired alkoxy substituted aminoquinoxalines (AQNX1-9) were synthesized by the reaction of QNX and alkoxy substituted aryl amines such as 2-methoxyaniline, 4-methoxyaniline, 2- ethoxyaniline, 3-ethoxyaniline, 4-ethoxyaniline, 4-butoxyaniline, 2,4-dimethoxyaniline, 3,4- dimethoxyaniline, and 3,5-dimethoxyaniline according to the previously published procedure. QNX was aminated in DMSO at 130°C. We synthesized various alkoxy-substituted aminoquinoxaline compounds (AQNX1-9) and evaluated their anticancer and antimicrobial activities in order to expand the search to related structures. In particular, two aminoquinoxaline (AQNX5 and AQNX6) compounds, coded as NSC D-835971/1 and NSC D-835972/1 by the National Cancer Institute in the USA, were screened for anticancer screening at a dose of 10-5 M on a full panel of 60 human cell lines obtained from nine human cancer cell types (leukemia, melanoma, non-small cell lung, colon, central (nervous system, ovarian, kidney, prostate, and breast cancer). Results: Further in silico studies were also conducted for the compound AQNX5 (NSC D- 835971/1), which was found to be the most active antiproliferative agent, especially against leukemia cell lines. Molecular docking studies showed that AQNX5 interacted with Glu286 and Lys271 through hydrogen bonding and π-stacking interaction in the ATP binding region of Abl kinase, which is indicated as a potential target of leukemia. Besides, AQNX5 occupied the minor groove of the double helix of DNA via π-stacking interaction with DG-6. Conclusion: According to in silico pharmacokinetic determination, AQNX5 was endowed with drug-like properties as a potential anticancer drug candidate for future experiments. In the light of these findings, more research will focus on aminated quinoxalines' ability to precisely target leukemia cancer cell lines.

Modulatory Effect of Cucurbitacin D from Elaeocarpus hainanensis on ZNF217 Oncogene Expression in NPM-Mutated Acute Myeloid Leukemia.

Background/Objectives: The expression of oncogene zinc-finger protein 217 (ZNF217) has been reported to play a central role in cancer development, resistance, and recurrence. Therefore, targeting ZNF217 has been proposed as a possible strategy to fight cancer, and there has been much research on compounds that can target ZNF217. The present work investigates the chemo-preventive properties of cucurbitacin D, a compound with a broad range of anticancer effects, in hematological cancer cells, specifically with regard to its ability to modulate ZNF217 expression. Methods: Different cucurbitacins were isolated from the Vietnamese plant Elaeocarpus hainanensis. The purified compounds were tested on nucleophosmin-mutated acute myeloid leukemia and other hematological cancer cell lines to assess their effects on the cell cycle, cell viability and apoptosis, and the expression of ZNF217. Results: Cucurbitacin D resulted in a reduction in the number of acute myeloid leukemia cells by inducing an increase in apoptosis and blocking cell cycle progression. It also led to a significant decrease in ZNF217 expression in the nucleophosmin-mutated acute myeloid leukemia cell line but not in the other hematologic cancer cell lines. The reduction in ZNF217 expression contributed significantly to the blocking of cell cycle progression but did not affect apoptosis. Conclusions: The obtained results suggest that cucurbitacin D is a promising molecule for targeting mutated nucleophosmin or its pathway in acute myeloid leukemia cells, although further studies are needed for in-depth investigations into its specific mechanisms.

Tumor Cell‐Specific Metabolic Labelling of Surface Sialoglycans and Post‐Click with Multivalent Rhamnose Enable Precise Immune Killing by Endogenous Antibody

Comprehensive SummaryWe report the design and development of a β‐glucuronidase (β‐Glu)‐responsive ManNAz derivative, Glu‐AAM, for tumor‐selective metabolic glycoengineering. Glu‐AAM enables specific labeling of tumor cell surface sialoglycans in the presence of overexpressed β‐Glu in cancer cells, including breast, leukemia, and colorectal cancer cells. We demonstrate the high selectivity and efficiency of Glu‐AAM‐mediated metabolic glycoengineering across multiple cancer cell lines. Furthermore, we synthesized multivalent antibody‐recruiting molecules (DBCO‐Rha) that can be covalently attached to the azido‐modified tumor cell surface, leading to potent antibody‐dependent cellular phagocytosis and complement‐dependent cytotoxicity. The octameric DBCO‐Rha8 construct exhibited the most effective immune response. This integrated strategy of β‐Glu‐responsive metabolic glycoengineering and antibody‐recruiting immunotherapy provides a promising platform for targeted cancer therapies and expands the toolbox of metabolic glycoengineering for cancer immunotherapy.

Development of Novel 1,3,4‐Trisubstituted Pyrazole Derivatives Bearing Sulfonamide Moiety as Anticancer Agents Targeting JNK Kinases

AbstractIn the present work, a new set of N‐(2‐((4‐(1,3‐diphenyl‐1H‐pyrazol‐4‐yl)pyridine sulfonamide derivatives was synthesized. Final target compounds were tested against JNK1 and JNK2 isoforms. Compounds 8f and 8d showed the highest activity over both JNK isoforms. They showed submicromolar activity over JNK1 (IC50 0.90 µM and 0.96 µM, respectively). They also showed excellent activity over JNK2 (IC50 0.62 µM and 1.07 µM, respectively). Moreover, the final target compounds were tested over HL‐60 and K‐562 cell lines for assessing the in vitro anticancer activity using sorafenib as a positive control. Compound 8f showed the highest potency at IC50 values of 6.21 and 7.43 µM, respectively. Furthermore, compounds 8e and 8g exhibited strong effects on both acute leukemia cancer cell lines with IC50 values of 13.83 and 10.02 µM, respectively, as well as chronic leukemia cancer cell line with IC50 of 12.65 and 9.51 µM, respectively. Compound 8f was also tested to examine its effect on the cell cycle. Finally, a molecular docking study was conducted to understand the plausible binding modes of the most active compounds 8d and 8f within the JNK1 and JNK2 binding sites.

Targeting caspase-8/c-FLIPL heterodimer in complex II promotes DL-mediated cell death.

Death receptor (DR) networks are controlled by the assembly of the Death-Inducing Signaling Complex (DISC) and complex II. The family of small molecules FLIPins (FLIP interactors) were developed to target the caspase-8/c-FLIPL heterodimer. FLIPin compounds were shown to promote apoptosis and caspase-8 activation at the DISC upon stimulation with death ligands (DLs) such as CD95L and TRAIL. To further investigate the role of FLIPin compounds in the DL-mediated cell death response, we analyzed their effects in combination with DLs and SMAC mimetics treatment. FLIPins were found to enhance cell viability loss and cell death induced by DL and SMAC mimetics in acute myeloid leukemia (AML), colon and pancreatic cancer cells. FLIPins enhanced both DL/BV6-induced apoptosis and DL/BV6/zVAD-fmk-induced necroptosis via an increase in complex II formation. Our results indicate that targeting the caspase-8/c-FLIPL heterodimer plays a prominent role in enhancing cell death induced by co-stimulation of DL/SMAC mimetics and opens new therapeutic strategies for targeting DR networks.

Features of Usp1 expression and localization in different types of malignant neoplasms

Aim. Malignant neoplasms pose a significant challenge in medicine, requiring a deep understanding of the molecular mechanisms underlying their pathogenesis. This study aimed to investigate the expression profile and subcellular localization of ubiquitin-specific protease 1 (USP1) in various types of cancer. Methods. Using the TCGA database, an analysis of USP1 expression was conducted across different cancer types. Immunofluorescence analysis with confocal microscopy was utilized to determine the subcellular localization of USP1 in chronic myeloid leukemia (CML) and prostate cancer cells. Results. Bioinformatic analysis revealed heterogeneous USP1 expression, with increased levels observed in acute myeloid leukemia, esophageal carcinoma, and glioblastoma multiforme. Immunofluorescence analysis confirmed nuclear localization of USP1 in CML cells and showed that inhibiting USP1 interaction with UAF1 using ML323 disrupts its transport to the nucleus. Prostate cancer cells exhibited both nuclear and atypical cytoplasmic USP1 localization, suggesting alterations in its expression, interaction with UAF1, and disruption of signaling pathways. Conclusions. USP1 plays a multifaceted role in cancer processes, with dysregulation of its expression and localization associated with tumorigenesis. Targeting USP1 holds therapeutic potential for cancer treatment.

Paulownin elicits anti-tumor effects by enhancing NK cell cytotoxicity through JNK pathway activation.

Paulownin, a natural compound derived from Paulownia tomentosa wood, exhibits various physiological functions, including anti-bacterial and anti-fungal effects. However, the impact of paulownin on natural killer (NK) cell immune activity remains largely unknown. In this study, we investigated the effect of paulownin on NK cell activity both in vitro and in vivo, and explored its potential mechanisms. NK-92 cells were used for in vitro experiments and a BALB/c mouse model with B16F10 cells injected subcutaneously were used for in vivo anti-tumor analysis. We found that paulownin enhanced the cytolytic activity of NK-92 cells against leukemia, human colon, and human lung cancer cell lines. Paulownin treatment increased the expression of the degranulation marker protein CD107a and cytolytic granules, including granzyme B and perforin in NK-92 cells. Moreover, these enhancements of cytotoxicity and the expression of cytolytic granules induced by paulownin were also observed in human primary NK cells. Signaling studies showed that paulownin promoted the phosphorylation of JNK. The increased perforin expression and elevated cytotoxic activity induced by paulownin were effectively inhibited by pre-treatment with a JNK inhibitor. In vivo studies demonstrated that the administration of paulownin suppressed the growth of B16F10 melanoma cells allografted into mice. Paulownin administration promoted the activation of NK cells in the spleen of mice, resulting in enhanced cytotoxicity against YAC-1 cells. Moreover, the anti-tumor effects of paulownin were reduced upon the depletion of NK cells. Therefore, these results suggest that paulownin enhances NK cell cytotoxicity by activating the JNK signaling pathway and provide significant implications for developing new strategies for cancer immunotherapy.

1,3-Disubstituted thiourea derivatives: Promising candidates for medicinal applications with enhanced cytotoxic effects on cancer cells

The distinct chemical structure of thiourea derivatives provides them with an advantage in selectively targeting cancer cells. In our previous study, we selected the most potent compounds, 2 and 8, with 3,4-dichloro- and 3-trifluoromethylphenyl substituents, respectively, across colorectal (SW480 and SW620), prostate (PC3), and leukemia (K-562) cancer cell lines, as well as non-tumor HaCaT cells. Our research has demonstrated their anticancer potential by targeting key molecular pathways involved in cancer progression, including caspase 3/7 activation, NF-κB (Nuclear Factor Kappa-light-chain-enhancer of activated B cells) activation decrease, VEGF (Vascular Endothelial Growth Factor) secretion, ROS (Reactive Oxygen Species) production, and metabolite profile alterations. Notably, these processes exhibited no significant alterations in HaCaT cells. The effectiveness of the studied compounds was also tested on spheroids (3D culture). Both derivatives 2 and 8 increased caspase activity, decreased ROS production and NF-κB activation, and suppressed the release of VEGF in cancer cells. Metabolomic analysis revealed intriguing shifts in cancer cell metabolic profiles, particularly in lipids and pyrimidines metabolism. Assessment of cell viability in 3D spheroids showed that SW620 cells exhibited better sensitivity to compound 2 than 8. In summary, structural modifications of the thiourea terminal components, particularly dihalogenophenyl derivative 2 and para-substituted analog 8, demonstrate their potential as anticancer agents while preserving safety for normal cells.

Synthesis of Novel Benazepril-Derived Trizole Compounds Assisted by Ultrasound: In Vitro and In Silico Analysis for Potential Anticancer Properties.

Benazepril-based novel trizole derivatives are being explored as potential anticancer agents, designed with an N-substituted 1,2,3-triazole moiety linked to Benazepril's N-1 position via a methylene bridge. An ultrasound irradiated CuAAC method was used to prepare all these compounds and evaluated their anti-proliferative activities against cancer and drug-resistant cell lines. While some of these compounds demonstrated anti-proliferative activity towards leukemic cancer cell line K562, two of them displayed complete inhibitory activity. Interestingly, the compounds 5n and 5o showed potent activity against imatinib-resistant cell lines suggesting their promise to overcome cancer drug resistance. Furthermore, molecular docking analysis revealed that compounds 5n and 5o have higher predicted sensitivity towards ACE protein when compared to benazepril and lisinopril indicating their value as potential drug lead molecules. This research introduces a distinctive approach by employing ultrasound to facilitate CuAAC reactions in medicinal chemistry.

An investigation of quantum dot theranostic probes for prostate and leukemia cancer cells using a CdZnSeS QD-based nanoformulation

Anticancer theranostic nanocarriers have the potential to enhance the efficacy of pharmaceutical evaluation of drugs. Semiconductor nanocrystals, also known as quantum dots (QDs), are particularly promising components of drug carrier systems due to their small sizes and robust photoluminescence properties. Herein, bright CdZnSeS quantum dots were synthesized in a single step via the hot injection method. The particles have a quasi-core/shell structure as evident from the high quantum yield (85 %), which decreased to 41 % after water solubilization. These water solubilized QDs were encapsulated into gallic acid / alginate (GA-Alg) matrices to fabricate imaging QDs@mod-PAA/GA-Alg particles with enhanced stability in aqueous media. Cell viability assessments demonstrated that these nanocarriers exhibited viability ranging from 63 % to 83 % across all tested cell lines. Furthermore, the QDs@mod-PAA/GA-Alg particles were loaded with betulinic acid (BA) and ceranib-2 (C2) for in vitro drug release studies against HL-60 leukemia and PC-3 prostate cancer cells. The BA loaded QDs@mod-PAA/GA-Alg had a half-maximal inhibitory concentration (IC50) of 8.76 μg/mL against HL-60 leukemia cells, which is 3-fold lower than that of free BA (IC50 = 26.55 μg/mL). Similar enhancements were observed with nanocarriers loaded with C2 and simultaneously with both BA and C2. Additionally, BA:C2 loaded QDs@mod-PAA/GA-Alg nanocarriers displayed a similar enhancement (IC50 = 3.37 μg/mL compared against IC50 = 11.68 μg/mL for free BA:C2). The C2 loaded QDs@mod-PAA/GA-Alg nanocarriers had an IC50 = 2.24 μg/mL against HL-60 cells. C2 and BA loaded QDs@mod-PAA/GA-Alg NCr had IC50 values of 7.37 μg/mL and 24.55 μg/mL against PC-3 cells, respectively.

Thiobenzamide-based ruthenium complexes: chemical reactivity and promising biological investigations against Leukemia cancer cells

Thiobenzamide-based ruthenium complexes: chemical reactivity and promising biological investigations against Leukemia cancer cells

Hesperidin/Salinomycin Combination; a Natural Product for Deactivation of the PI3K/Akt Signaling Pathway and Anti-Apoptotic Factors in KG1a Cells.

AML is a highly aggressive malignant clonal disease of hematopoietic origin. Hesperidin as a polyphenol glycoside, Activates the apoptotic pathway and salinomycin as a k + selective ionophore. We examined how hesperidin and salinomycin induce pro-apoptotic effects in KG1a cells. Cells were divided into four groups; 1) control cells (CRTL), 2) cells treated with hesperidin 85μM, 3) cells treated with 2μM salinomycin, 4) cells treated with combination of salinomycin and hesperidin. The MTT assay was implemented to determine the IC50 of hesperidin and salinomycin in KG1a cell lines. Propidium iodide staining and flow cytometry were used to analyze the distribution of the cell cycle. The level of ROS was evaluated by fluorescent microscopy and spectrophotometry. Additionally, Akt, XIAP, Bad, and FOXO1 gene expression was analyzed by real-time PCR. Hesperidin/Salinomycin decreased the viability of KG1a leukemic cells more than Hesperidin and Salinomycin separately. Changes in the shape of apoptotic cells and rise in ROS levels were detected after Hesperidin/Salinomycin treatment. Our findings showed that following Hesperidin/Salinomycin treatment, the expression of PI3K/AKT signaling pathway related genes (AKT, PTEN and FOXO1), were in line with the destruction of KG-1a cells. Furthermore, XIAP and BAD mRNA were regulated to trigger apoptosis in cancer cells. The study discovered that hesperidin and salinomycin, could effectively hinder the PI3K/Akt signaling pathway in leukemia cancer cells. Also, the combination of hesperidin and salinomycin has the potential to be a treatment option for acute myeloid leukemia.

Dynamics of nucleoplasm in human leukemia cells: A thrust towards designing anti-leukemic agents

The human inosine monophosphate dehydrogenase (hIMPDH) is a metabolic enzyme that possesses a unique ability to self-assemble into higher-order structures, forming cytoophidia. The hIMPDH II isoform is more active in chronic myeloid leukemia (CML) cancer cells, making it a promising target for anti-leukemic therapy. However, the structural details and molecular mechanisms of the dynamics of hIMPDHcytoophidia assembly in vitro need to be better understood, and it is crucial to reconstitute the computational nucleoplasm model with cytophilic-like polymers in vitro to characterize their structure and function. Finally, a computational model and its dynamics of the nucleoplasm for CML cells have been proposed in this short review. This research on nucleoplasm aims to aid the scientific community's understanding of how metabolic enzymes like hIMPDH function in cancer and normal cells.However, validating and justifying the computational results from modeling and simulation with experimental data is essential. The new insights gained from this research could explain the structure/topology, geometrical, and electronic consequences of hIMPDH inhibitors on leukemic and normal cells. They could lead to further advancements in the knowledge of nucleoplasmic chemical reaction dynamics.

Prospects for Prostate Cancer Chemotherapy: Cytotoxic Evaluation and Mechanistic Insights of Quinolinequinones with ADME/PK Profile.

The evaluation of in vitro biological activity of several previously reported quinolinequinones (AQQ1-5) against 60 human cancer cell lines (NCI-60) used by the National Cancer Institute's Developmental Therapeutics Program (DTP) contributed to our earlier research on possible anticancer and/or antibacterial agents. Of interest, NCI-60 screening revealed that two quinolinequinones (AQQ1 and AQQ2) significantly reduced the proliferation of several cancer genotypes. Following the administration of a single dose and five additional doses, all quinolinequinones demonstrated a significant inhibitory effect on the growth of leukemia and other cancer cell lines. Hence, a series of subsequent in vitro biological assessments were performed to further understand the mechanistic impact of the compounds. In MTT assays, it was found that AQQ1 and AQQ2 exhibited higher efficacy against DU-145 cells (IC50 4.18 µM and 4.17 µM, respectively) compared to MDA-MB-231 (IC50 8.27 and 13.33 µM, respectively) and HCT-116 cells (IC50 5.83 and 9.18 µM, respectively). Additionally, AQQ1 demonstrated greater activity in this context. Further investigations revealed that AQQ1 inhibited DU-145 cell growth and migration dose-dependently. Remarkably, arrest of the DU-145 cell cycle at G0/G1 phase and ROS elevation were observed. Pharmacokinetic (PK) studies revealed that AQQ1 has better PK parameters than AQQ2 with %F of 9.83 in rat. Considering the data obtained with human liver microsomal stability studies, AQQ1 should have a better PK profile in human subjects. In silico studies (molecular dynamics) with three kinases (CDK2, CDK4, and MAPK) leading to cell cycle arrest at G0/G1 identified MAPK as a probable target for AQQ1. Taken together, our results showed that AQQ1 could be a potential chemotherapeutic lead molecule for prostate cancer.

Facile Synthesis of a Crystalline Zinc Sulfide/Chitosan Biopolymer Nanocomposite: Characterization and Application for Photocatalytic Degradation of Textile Dyes and Anticancer Activity.

In the present study, we have synthesized a zinc sulfide/chitosan (ZS/CS) nanocomposite by utilizing simple, economical, and environmentally friendly methods. The synthesized nanomaterials were characterized by different analytical techniques such as XRD, FE-SEM, EDS, and FTIR to determine the phase structure, morphology, and elemental composition. FTIR spectroscopy was used to confirm the functional groups of the synthesized zinc sulfide (ZS) nanoparticles and ZS/CS composite. Besides, the optical properties of the as-synthesized nanocomposite was analyzed by a UV-visible spectrophotometer, and the estimated band gap energy is ∼3.03 eV. The photocatalytic efficiency of the synthesized ZS/CS nanocomposite was investigated against two textile dyes, Crystal Violet (CV) and Acid Red-I (AR-I), under UV-visible light irradiation. The nanocomposite showed excellent photocatalytic activity against the dyes, and photodegradation was estimated to be about 93.44 and 90.67% for CV and AR-I, respectively. The nanocomposite was reused for three consecutive cycles. The results revealed that the photocatalyst displayed good reusability during the photocatalytic decomposition and thus is considered a cost-effective and promising photocatalyst in degrading dye pollutants. The kinetic study proved that the pseudo-first-order reaction kinetics was followed by the degradation process. We also examined the anticancer activity of ZS and ZS/CS against human breast and myelogenous leukemia cancer cell lines, namely, MCF-7 and K-562, and the half minimal inhibitory concentrations were found to be less than 50 μg/mL.