Non-cancerous Cell Line Research Articles

Triterpenoid phthalimides as selective anti-cancer agents targeting mitochondrial apoptosis.

Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized and subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, and related derivatives. A total of 55 new compounds were prepared and tested for in vitro cytotoxic activity against eight cancer cell lines and two non-cancerous cell lines. Four compounds with IC50 values of 5μM or lower were selected for further investigation. These compounds induced apoptosis in CCRF-CEM cells in a concentration-dependent manner, accompanied by mitochondrial depolarization and altered expression of key proteins involved in mitochondrial apoptosis. The compounds also disrupted DNA replication and transcriptional activity. Modulation of key proliferation pathways, including PI3K/Akt and STAT3, further supported the antiproliferative potential of these derivatives. Considering their high cytotoxicity and antiproliferative activity in CCRF-CEM cells, compounds 19, 26, 28, and 30 have been identified as promising candidates for further development.

Analysing DNA methylation and transcriptomic signatures to predict prostate cancer recurrence risk.

Prostate cancer (PCa) remains a significant global health challenge, with approximately 1.6 million new cases and 366,000 deaths annually. Despite high survival rates for localized prostate cancer, recurrence poses a substantial risk due to inherent biological factors and residual disease. Early detection and intervention are essential for enhancing patient outcomes and reducing mortality. However, traditional diagnostics such as PSA tests, digital rectal examinations, and biopsies often lack specificity resulting in overdiagnosis. There is a pressing need for novel biomarkers to enhance precision medicine approaches for PCa. This study employs a machine learning approach to identify DNA methylation and RNA expression biomarkers predictive of PCa recurrence using datasets from The Cancer Genome Atlas (TCGA). We analyzed 49,133 genes, identifying 684 differentially methylated genes (DMGs) and 691 differentially expressed genes (DEGs) between recurrence and non-recurrence groups. Ten genes (TNNI2, SPIN2, COL5A3, RNF169, CCND1, FGFR1, SLC17A2, FAMM71F2, RREB1, AOX1) were found to have significant correlations between methylation and expression, forming the basis for our predictive model. A support vector machine (SVM) model was developed using these ten genes, achieving an area under the curve (AUC) of 0.773, demonstrating robust predictive capability. Multivariate regression analysis confirmed the SVM score as an independent predictor of recurrence (HR = 0.45; 95% CI 0.28-0.69, P < 0.001). The analysis of recurrence-free survival suggested that patients with low-risk scores experienced significantly better outcomes compared to those with high-risk scores. Functional enrichment analyses of DMGs revealed significant involvement in biological processes such as transcription regulation, signal transduction, and immune response, highlighting the potential mechanistic pathways of these biomarkers. Validation using real-time PCR confirmed differential expression and methylation patterns of the identified genes in prostate cancer (PC3) and non-cancerous cell lines (PNT2). In conclusion, our study hihglights the DNA methylation biomarkers linked to PCa recurrence and introduces a promising SVM model for early prediction, potentially improving treatment outcomes. Further research is needed to explore the biological roles of these genes in PCa aiming to refine therapeutic approaches.

Chromatin Marks H3K4me3 and H3K9me3 in Triple-Negative Breast Cancer Cell Lines.

Triple-negative breast cancer (TNBC) is the most lethal and aggressive breast cancer among all the breast cancer subtypes. Despite several attempts, to date, there is an extensive lack of therapeutic intervention. Hence, there is a dire need for an effective biomarker to timely diagnose TNBC. Here, utilizing super-resolution microscopy, the remodeling structural aspects of euchromatin and heterochromatin in TNBC are studied and the results are compared with non-cancerous and non-TNBC cell lines. The nanoscopic visualization reveals a distinct difference in chromatin remodeling in TNBC in comparison to the other two cell lines. While the euchromatin density is found to increase, the heterochromatin is found to decrease. A complete switching of the heterochromatin-euchromatin ratio is observed in TNBC cells thus proposing that chromatin remodeling and chromatin morphological changes can be pursued as one of the targets for diagnostic purposes. Increased expression of structure specific recognition protein-1(SSRP-1) protein supports the increased rate of chromatin remodeling in breast cancer cell lines. The results may lead to developing a new strategy for diagnosing TNBC patients.

Phytochemical Profile and Anticancer Potential of Helichrysum arenarium Extracts on Glioblastoma, Bladder Cancer, and Breast Cancer Cells

Background/Objectives: Cancer is the second leading cause of death globally. Medicinal plants have emerged as fundamental sources of bioactive compounds with anticancer potential, largely attributed to their diverse secondary metabolites. This study aimed to investigate the cytotoxic effects of Helichrysum arenarium extracts from two distinct regions of Turkiye, Mersin, and Artvin, on cancerous (MDA-MB-231, RT4, T98G) and non-cancerous (ARPE-19, hGF) cell lines and to identify bioactive compounds responsible for these effects. Methods: H. arenarium plant extracts were prepared using ethanol and methanol as solvents, followed by lyophilization and dissolution in DMSO. The cytotoxic effects of the extracts were evaluated using Hoechst staining and MTS assays to assess cell viability. IC50 values and selectivity indices were calculated. Phytochemical composition was analyzed using Quadrupole Time-of-Flight mass spectrometry. Results: The ethanol extract from Mersin (HAE-M) demonstrated superior cytotoxicity, particularly against breast and bladder cancer cells, while showing minimal impact on non-cancerous cells. HAM-M, HAE-A, and HAM-A exhibited comparatively less potent effects. Phytochemical analysis of HAE-M identified 16 bioactive compounds, including Naringenin, Luteolin, and Quercitrin, known for their antioxidant and anticancer properties. Conclusions: These findings highlight the potential of H. arenarium extracts, particularly HAE-M, as a source of potent anticancer agents. This study is novel in its comprehensive analysis of different extraction methods and regional plant sources, combined with phytochemical profiling, to identify selective anticancer effects. Further investigations into the mechanisms of action of these extracts could contribute to the development of plant-derived anticancer therapies.

Synthesis and Anticancer Evaluation of O-Alkylated (E)-Chalcone Derivatives: A Focus on Estrogen Receptor Inhibition.

Cancer remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for novel therapeutic agents. This study investigated the synthesis and biological evaluation of O-alkyl (E)-chalcone derivatives (4a-4v) as potential anticancer agents. The compounds were synthesized via aldol condensation of substituted aldehydes and acetophenones, with structures confirmed by IR, NMR, and mass spectrometry. In vitro cytotoxicity assays revealed varying effectiveness, with compounds 4a, 4b, 4q, and 4v exhibiting potent activity against MDA-MB-231 and MCF-7, showing IC50 values between 2.08 and 13.58 µM, besides HCT-116 and HeLa cancer cell lines (IC50 values between 6.59 and 22.64 µM). Notably, compound 4b displayed remarkable selectivity, with an IC50 of 54.59 µM against the non-cancerous WI-38 cell line. Additionally, protein kinase inhibition assays indicated that compounds 4b and 4q effectively inhibited EGFR and VEGFR-2, with 4b outperforming the standard inhibitor erlotinib. Molecular docking studies of compound 4q showed strong binding affinities in the ATP-binding pockets of EGFR, HER2, VEGFR2, and CDK2. In silico analyses further highlighted the favorable pharmacokinetic properties of compound 4q, underscoring its potential as a selective tyrosine kinase inhibitor. These findings suggest the therapeutic promise of O-alkyl (E)-chalcone derivatives in cancer treatment.

Novel aryl (dithioglycosyl)methane derivatives as anti-proliferative agents.

In a quest of developing carbohydrate derived anti-cancer agents, novel carbohydrate dithioacetal derivatives have been synthesized and evaluated for their potential as anti-proliferative agents against breast cancer cell lines (MCF-7 and MDA-MB-231) as well as non-cancerous kidney epithelial cell line (NKE). Total 18 compounds have been screened and 3 compounds showed promising anti-proliferative activities against cancer cells with low cytotoxicity to the normal cells using MTT assay. The mode of action of the best active compound has been proposed based on several microscopic studies. A molecular docking study also confirmed the proposed mechanism for the anti-proliferative properties.

Functionalized regioisomers of the natural product phenazines myxin and iodinin as potent inhibitors of Mycobacterium tuberculosis and human acute myeloid leukemia cells.

The natural bioactive products myxin and iodinin are phenazine 5,10-dioxides possessing potent anti-bacterial and anti-cancer activity in vitro. This work describes the synthesis and derivatization of new myxin and iodinin regioisomers, developed from 1,3-dihydroxyphenazine 5,10-dioxide. Compounds were evaluated for activity towards M. tuberculosis (Mtb) strains, a human AML cell line (MOLM-13), and two non-cancerous mammalian cell lines (NRK and H9c2). Highly potent analogs were developed having IC50 values against MTB down to 20nM and 1.4μM for human AML cells. 1-OH-3-O-alkyl substituted derivatives demonstrated high efficacy against Mtb and low toxicity in normal cells. 2,3-substituted regioisomers of myxin and iodinin were shown to be inactive, highlighting the importance of oxygen substituent in position 1 of the scaffold. A strong positive correlation between anti-MTB and anti-AML activity was revealed, suggesting a common mechanism of action in bacteria and cancer cells. These findings demonstrate the therapeutic potential of 1,3-O-functionalized phenazine 5,10-dioxides in chemotherapy for Mtb and AML and contribute to the structure-activity understanding of phenazine 5,10-dioxides with respect to their biological activity.

Investigation of Cytotoxic Activity of Anthriscus nemorosa (M.Bieb.) Spreng. on Lung Cancer Cells

Medicinal plants are considered an important source of human health due to their therapeutic potential against various diseases including cancer. Cancer is a life-threatening disease characterized by uncontrolled cell growth and abnormal signaling processes. The incidence of cancer in society is increasing day by day. The search for active biological resources is important for the discovery of new anticancer drugs. Anthriscus nemorosa (M.Bieb.) Spreng. (Apiaceae) is a medicinal plant naturally distributed in Turkiye and traditionally used as food and against various diseases. This study investigated the methanol extracts of aerial parts and roots of A. nemorosa for cytotoxicity on lung cancer (A549) and non-cancerous (L929) cell lines. According to the results, both extracts showed significant dose-dependent cytotoxic effects on lung cancer cells. IC50 value was recorded as 8.29 μg/mL in the aerial parts extract. On the other hand, it was recorded as 3.57 μg/mL in the roots extract. Furthermore, the selectivity indexes were calculated as 5.93 and 3.38 for aerial parts and roots extracts, respectively. In light of the findings, it has been concluded that A. nemorosa deserves further anticancer research

A First Report of Docosahexaenoic Acid‐Clocked Polymer Enveloped Gold Nanoparticles: A Way to Precision Breast Cancer and Triple Negative Breast Cancer Therapy and Its Apoptosis Induction

ABSTRACTFunctionalized gold nanoparticles (GNPs) are extensively utilized in various disciplines due to their excellent bioactivity, biocompatibility, and extended drug half‐life, influenced by the ligands and size that are changed on surfaces. In this study, we successfully fabricated GNPs coated with ligands containing docosahexaenoic acid (DHA) and polyethylene glycol (PEG) clocked by a carboxyl group. These nanoparticles are referred to as MPA@GNPs‐PEG‐DHA. The cytotoxicity results demonstrate that MPA@GNPs‐PEG‐DHA exhibits superior cell selectivity, explicitly inhibiting the proliferation of breast cancerous cells than noncancerous cell lines. Apoptosis is involved in the reduction of cell proliferation by MPA@GNPs‐PEG‐DHA, as demonstrated clearly through many assays measuring apoptotic index, including AO/EB staining, DAPI, annexin V‐FITC staining, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) measurement. The efficacy of MPA@GNPs‐PEG‐DHA in inducing apoptosis was demonstrated by its inhibition of mitochondrial dysfunction by ROS. MPA@GNPs‐PEG‐DHA has the potential to improve the induction of apoptosis in breast cancerous cells.

Phosphine Oxide Indenoquinoline Derivatives: Synthesis and Biological Evaluation as Topoisomerase I Inhibitors and Antiproliferative Agents.

The synthesis of phosphorous indenoquinolines and their biological evaluation as topoisomerase 1 (TOP1) inhibitors and antiproliferative agents were performed. First, the preparation of new hybrid 5H-indeno[2,1-c]quinolines with a phosphine oxide group was performed by a two-step Povarov-type [4+2]-cycloaddition reaction between the corresponding phosphorated aldimines with indene in the presence of BF3·Et2O. Subsequent oxidation of the methylene present in the structure resulted in the corresponding indeno[2,1-c]quinolin-7-one phosphine oxides 10. The synthesized derivatives were evaluated as TOP1 inhibitors showing higher inhibition values than CPT at prolonged incubation times (5 min). Inhibition of TOP1 was even observed after 30 min of incubation. The cytotoxic activities of these compounds were also studied against different cancer cell lines and a non-cancerous cell line. While some compounds showed cytotoxicity against some cancerous cells, none of the compounds showed any cytotoxicity against the non-cancerous cell line, MRC-5, in contrast to CPT, which exhibits high toxicity against this cell line. These results represent a very interesting advance since the heterocyclic phosphine oxide derivatives have important properties as TOP1 inhibitors and show an interesting cytotoxicity against different cell lines.

Apoptosis-Inducing Activity of a 2-Hydroxyphenyl Benzamide-Based Self-Assembled Anion Channel.

Despite the significant interest in designing artificial ion channels, there is limited availability of channel-forming molecules to tackle complex issues, especially in biological systems. Moreover, a major challenge is the scarcity of chloride transporters that can selectively induce toxicity in cancer cells while minimizing harm to normal healthy cells. This work reports a series of 2-hydroxyphenyl benzamide-based small molecules 1 a-1 c, which self-assemble to form barrel rosette-type artificial ion channels that adequately transport chloride ions across membranes. The formation of these ion channels primarily relies on intermolecular hydrogen bonding and π-π stacking interactions, as supported by the analysis of single-crystal X-ray diffraction and molecular dynamics (MD) simulations. Importantly, chloride ion transport by these compounds specifically triggers apoptosis in cancer cells while demonstrating relatively low toxicity toward non-cancerous cell lines.

Shift of cell-death mechanisms in primary human neutrophils with a ruthenium photosensitizer.

Primary human neutrophils are the most abundant human white blood cells and are central for innate immunity. They act as early responders at inflammation sites, guided by chemotactic gradients to find infection or inflammation sites. Neutrophils can undergo both apoptosis as well as NETosis. NETosis is a form of neutrophil cell death that releases chromatin-based extracellular traps (NETs) to capture and neutralize pathogens. Understanding or controlling the balance between these cell-death mechanisms is crucial. In this study, the chemical synthesis and biologic assessment of a ruthenium complex as a light-activated photosensitizer that creates reactive oxygen species (ROS) in primary human neutrophils is reported. The ruthenium complex remains non-toxic in the dark. However, upon exposure to blue light at 450nm, it exhibits potent cytotoxic effects in both cancerous and non-cancerous cell lines. Interestingly, the metal complex shifts the cell-death mechanism of primary human neutrophils from NETosis to apoptosis. Cells irradiated directly by the light source immediately undergo apoptosis, whereas those further away from the light source perform NETosis at a slower rate. This indicates that high ROS levels trigger apoptosis and lower ROS levels NETosis. The ability to control the type of cell death undergone in primary human neutrophils could have implications in managing acute and chronic infectious diseases.

Cytotoxic effects of the standardized extract from Curcuma aromatica Salisb. rhizomes via induction of mitochondria-mediated caspase-dependent apoptotic pathway and p21-mediated G0/G1 cell cycle arrest on human gastric cancer AGS cells

ABSTRACT Curcuma aromatica Salisb. (C. aromatica) is one of the traditional herbs used to treat microbial infection, skin eruption, coronary heart disease, and other diseases, including cancer. However, the inhibitory effects and underlying mechanisms of action of C. aromatica on gastric cancer cells have not yet been fully elucidated. Our study aimed to examine the possible molecular mechanisms underlying the cytotoxic effects attributed to C. aromatica rhizome standardized extract against gastric cancer cells. The components of two major active compounds in C. aromatica rhizome extract were quantitatively analyzed using a simple and validated HPLC method. Cytotoxicity was determined in different gastric cancer and non-cancer cell lines. The biological activities of the extract targeting apoptosis and cell cycle-related genes on gastric cancer AGS cells were also investigated to elucidate the mechanisms relating to the anti-proliferative effect of C. aromatica rhizomes. The two major active compounds curdione and germacrone, in the C. aromatica extract were standardized to 0.64% and 1.12% w/w, respectively. The standardized extract (CAE) exerted cytotoxic effects on various cancer cells, whereas minimal effects at equivalent doses were noted for normal cells. CAE concentration-dependently suppressed growth of gastric cancer AGS cells via induction of apoptosis. Further studies revealed that CAE treatment disrupted mitochondrial membrane potential (ΔΨm), increased Bax/Bcl-2 ratio, and cytochrome c release, resulting in activation of caspase-9/-3 and subsequent cleavage of PARP. Further, the inhibitory effects of caspase-9/-3 expression by a synthetic pan-caspase inhibitor partially protected cells against apoptosis following CAE treatment. In addition, CAE significantly promoted cell death in AGS cells via an accumulation of cells in the G0/G1 phase. This effect was associated with upregulation of the CDK inhibitor p21 and downregulation of cyclin D1, cyclin E, CDK4, and CDK2 expression. Our data indicated that CAE exerted anti-proliferative activity by activating the mitochondria-mediated caspase-dependent apoptotic pathway and arresting the p21-mediated G0/G1 cell cycle on human gastric cancer AGS cells.

Small molecule protein assembly modulators with pan-cancer therapeutic efficacy.

Two structurally unrelated small molecule chemotypes, represented by compounds PAV-617 and PAV-951, with antiviral activity in cell culture against Mpox virus (formerly known as monkeypox virus) and human immunodeficiency virus (HIV) respectively, were studied for anti-cancer efficacy. Each exhibited apparent pan-cancer cytotoxicity with reasonable pharmacokinetics. Non-toxicity is demonstrated in a non-cancer cell line and in mice at doses achieving drug exposure at active concentrations. Anti-tumour properties of both chemotypes were validated in mouse xenografts against A549 human lung cancer and, for one of the chemotypes, against HT-29 colorectal cancer. The targets of these compounds are unconventional: each binds to a different transient, energy-dependent multi-protein complex. Treatment with these compounds alters the target multi-protein complexes in a manner that appears to remove a block, crucial for cancer survival and progression, on a homeostatic linkage between uncontrolled proliferation and apoptosis. These compounds provide starting points for development of novel, next-generation, non-toxic, pan-cancer therapeutics.

In vitro studies of the combination between berberine chloride and a Copper(II) complex against Triple negative breast cancer

In this study, the copper(II) complex [Cu(chromoneTSC)Cl2]•0·.5H2O•0.0625C2H5OH (where chromoneTSC = (E)-N-Ethyl-2-((4-oxo-4H-chromen-3-yl)methylene)-hydrazinecarbothioamide) was synthesized and characterized; then used to carry out in vitro studies in combination with berberine chloride (BBC). The ligand and complex were characterized by elemental analysis, FTIR and NMR (1H and 13C) spectroscopy, and conductivity measurements. The cytotoxic effect was analyzed by using the CCK-8 viability assay in cancer MDA-MB-231 VIM RFP and non-cancer MCF-10A cell lines. The IC50 values for the complex and BBC were 21.2 ± 1.6 and 48.3 ± 2.4 μM, respectively at 24 h incubation, while the IC50 value of the combination treatment was 9.3 ± 1.5 in cancer cells. The co-treatment group significantly increased the number of cells in G2 phase, indicating the growth arrest of cancer cells. Moreover, the combination group showed induction of both intrinsic and extrinsic apoptotic pathways. There was also a study on the effect of the combination treatment on receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL) as biomarkers of necroptosis. The results showed activation of necroptosis after treatment with the combination of the copper complex and BBC via the activation of RIPK3–MLKL pathway.

Molecular Hybrids of Quinoline and Sulfonamide: Design, Synthesis and in Vitro Anticancer Studies.

Molecular hybrids of diversely functionalized quinoline and sulfonamide have been designed. Multistep synthetic strategies have been used for the synthesis. The anti-cancer properties have been evaluated against various cancer cell lines including HCT116, A549, U2OS, CCRF-CEM, Jurkat, MOLT-4, RAMOS, and K562. Non-cancer cell lines MRC-5 and BJ were also included for comparison. When examining the effects on A549, HCT116, and U2OS cells, all tested compounds exhibited limited potency with IC50 values exceeding 50 μM, indicating weak activity against these cell lines. Against the ITK high cells Viz. are Jurkat, CCRF-CEM and MOLT-4, 9 e, 9 p and 9 j found to the maximum potent compounds with IC50 values of 7.43±7.40 μM, 13.19±1.25 μM and 5.57±7.56 μM respectively. Similarly, in the BTK high cells screenings, 9 n and 9 e molecules with an IC50 value of 2.76±0.79 μM and 5.47±1.71 μM against RAMOS and K562 respectively are highly potent. Interestingly, all the molecules have exhibited IC50 value >50 μM against the non-cancer cells (MRC-5 and BJ), which indicates the promising non-cytotoxic nature of the molecules.

In Vitro Anticancer Effects of Aqueous Leaf Extract from Nepeta nuda L. ssp. nuda.

Despite significant efforts, cancer remains the second leading cause of mortality worldwide. The medicinal plant Nepeta nuda L. represents a valuable source of biologically active compounds with pharmacological activities including antioxidant, anti-inflammatory, antimicrobial, and antiviral. This study aimed to assess the antiproliferative potential and mechanisms of action of aqueous extract from the leaves of wild-grown N. nuda. Cancer cell lines, MDA-MB-231, MCF7 (breast), HT29, Colon 26 (colon), and HepG2 (liver cancer), and a non-cancerous skin cell line, BJ, were assessed for antiproliferative activity by MTT assay and observation of cell morphological alterations. The cancer cell line that was most sensitive to the extract was further studied for apoptotic alterations by Annexin V/propidium iodide staining, colony-forming assay, and qRT-PCR analysis. The results revealed that the plant extract inhibited the proliferation of all investigated cancer cell lines with the strongest cytostatic effect on Colon 26 cells with a half maximal inhibitory concentration (IC50) value of 380.2 μg/mL and a selectivity index (SI) of 3.5. The extract significantly inhibited the ability of cells to form colonies, exhibited considerable proapoptotic potential involving the participation of the CASP8 gene, and increased the expression levels of ATG3 and the BECN1 gene, which suggests a role of autophagic cell death in the antitumor action.

Liposomes loaded with daunorubicin and an emetine prodrug for improved selective cytotoxicity towards acute myeloid leukaemia cells

The backbone of induction therapy in acute myeloid leukaemia (AML) is to use an anthracycline in combination with cytarabine. Despite recent advances in AML therapy, this treatment remains the standard, and it has been largely unchanged for decades. There are few curative options for patients unfit for this treatment. The anti-protozoal agent emetine improves efficacy of anthracycline treatment towards AML in vitro and in vivo but the effect is more potent when emetine is administered 30 minutes after anthracyclines. To delay the onset of protein synthesis inhibition we produced a novel inactive emetine prodrug and co-encapsulated this with the anthracycline daunorubicin (DNR) in liposomes. Nanoencapsulation protects the prodrug from degradation in the blood and ensure simultaneous delivery of both drugs to cancer cells. The prodrug concept will delay the onset of action of emetine relative to DNR. In AML cells, the combination of DNR and the emetine-prodrug in liposomes increased cytotoxicity compared to liposomes with DNR and native emetine. Liposomes loaded with the emetine prodrug did not show increased toxicity towards non-cancerous cell lines and zebrafish larvae. In patients, a liposomal formulation such as that presented herein could allow for a reduced DNR dose without compromising efficacy, thereby reducing toxic side effects and enabling improved therapy for patients not fit for current treatment options.

POCOP-Ni(II) pincer compounds derived from phloroglucinol. Cytotoxic and antioxidant evaluation.

POCOP-Ni(II) pincer compounds have primarily been explored as catalysts, but their potential biological activity has been scarcely studied. To address this gap, we evaluated the anticancer and antioxidant potential of four POCOP-Ni(II) complexes derived from phloroglucinol. A comprehensive supramolecular analysis, based on single-crystal X-ray diffraction (DRX) structures, was conducted using Hirshfeld surfaces and non-covalent interaction analysis. The cytotoxicity of all complexes was systematically assessed against various cancerous cell lines, as well as a non-cancerous cell line (COS-7). The results revealed that complexes 1b and 1c exhibited remarkable antiproliferative activity, with IC50 values ranging from 2.43 to 7.85μM against cancerous cell lines U251, K562, HCT-15, MCF-7, and SK-LU-1. To further elucidate their mechanism of action, a competitive fluorescence displacement assay with ethidium bromide (EB) suggested that these complexes possess the ability to intercalate with DNA. This multifaceted investigation not only enhances our understanding of the biological potential of POCOP-Ni complexes but also provides valuable insights into their structural features and interactions, paving the way for future exploration in both catalytic and therapeutic domains.

Characterization of novel ACE2 mRNA transcripts: The potential role of alternative splicing in SARS-CoV-2 infection

The human angiotensin converting enzyme 2 (ACE2) gene encodes a type I transmembrane protein, which is homologous to angiotensin I-converting enzyme (ACE) and belongs to the angiotensin-converting enzyme family of dipeptidyl carboxypeptidases. As highlighted by the COVID-19 pandemic, ACE2 is not only crucial for the renin-angiotensin-aldosterone system (RAAS), but also displays great affinity with the SARS-CoV-2 spike protein, representing the major receptor of the virus. Given the significance of ACE2 in COVID-19, especially among cancer patients, the present study aims to explore the transcriptional landscape of ACE2 in human cancer and non-cancerous cell lines through the design and implementation of a custom targeted long-read sequencing approach. Bioinformatics analysis of the massive parallel sequencing data led to the identification of novel ACE2 mRNA splice variants (ACE2 sv.7–sv.12) that demonstrate previously uncharacterized exon-skipping events as well as 5′ and/or 3′ alternative splice sites. Demultiplexing of the sequencing data elucidated the differential expression profile of the identified splice variants in multiple human cell types, whereas in silico analysis suggests that some of the novel splice variants could produce truncated ACE2 isoforms with altered functionalities, potentially influencing their interaction with the SARS-CoV-2 spike protein. In summary, our study sheds light on the complex alternative splicing landscape of the ACE2 gene in cancer cell lines, revealing novel splice variants that could have significant implications for SARS-CoV-2 susceptibility in cancer patients. These findings contribute to the increased understanding of ACE2′s role in COVID-19 and highlight the importance of considering alternative splicing as a key factor in viral pathogenesis. Undoubtably, further research is needed to explore the functional roles of these variants and their potential as therapeutic targets in the ongoing fight against COVID-19.