2025
Permanent URI for this collectionhttps://dl.bhu.ac.in/bhuir/handle/123456789/62057
Browse
Search Results
Now showing 1 - 6 of 6
PublicationBook Chapter Cell cycle arrest and apoptosis in glioblastoma(Elsevier, 2025) Sunanda Kulshrestha; Rohit Sharma; Alexiou T. AthanasiosGlioblastoma (GBM) is a quite aggressive and common form of brain tumor, which represents it as one of the lethal cancers for older age groups. GBM develops from gliomas, which are malignancies of soft tissues that progress to solid tumors. The median life expectancy is 15 months because of the terrible prognosis, which is accompanied by fast growth and a high recurrence tendency. Chemotherapy (temozolomide), radiotherapy, and surgical interventions all part of the standard treatment regimen. Newer methods like integration of medicine with immunotherapy and engineered technology therapy are also being investigated, but their effectiveness is still limited, leading to less-than-ideal prognoses. The GBM cells exhibit significant heterogeneity; adjuvant treatment may work for some GBM cells but not others, whether they are mature or stem cells, and this discrepancy could lead to tumor recurrence in the future. In addition, the aggressive prognosis of the cancer accounts to the significant obstacles to standard treatment methods because of the immunosuppressive microenvironment of the tumor cells. GBMs get their hands on the patients’ inherent biological abilities so they can keep on invasively growing and spreading. The majority of the time, this impacts the pathways that control cell cycle progression and cell death. The present review provides a brief overview of the mechanisms involved in cell growth regulation and GBM-specific dysregulation of the cell cycle and apoptosis along with the studied and experimental interventions related to the discovery of therapeutic agents targeting cellular cycle and inducing apoptosis. © 2026 Elsevier Inc. All rights reserved..PublicationArticle Chitosan-Functionalized Fluorescent Calcium Carbonate Nanoparticle Loaded with Methotrexate: Future Theranostics for Triple Negative Breast Cancer(American Chemical Society, 2025) Rinki Verma; Md Zeyaullah; Virendra Pratap Singh; Preeti Suman Saxena; Biplob Koch; Manoj KumarHerein, fluorescent calcium carbonate nanoclusters encapsulated with methotrexate (Mtx) and surface functionalized with chitosan (25 nm) (@Calmat) have been developed for the imaging and treatment of triple-negative breast cancer (TNBC). These biocompatible, pH-sensitive nanoparticles demonstrate significant potential for targeted therapy and diagnostic applications. The efficacy of nanoparticles (NPs) was evaluated in MDA-MB-231 TNBC cell lines. The enhanced permeability and retention effect facilitated the accumulation of NPs, in tumor-bearing rats, as confirmed by in vivo fluorescence imaging. Treatment with @Calmat resulted in a marked reduction in pro-inflammatory cytokines, with levels of IL-6 (1225 ± 67 pg/mL), IL-1β (379 ± 69 pg/mL), and TNF-α (14.1 ± 2 pg/mL), in contrast to the diseased control group (IL-6: 2223 ± 99; IL-1β: 1632 ± 90; TNF-α: 40 ± 3 pg/mL). A similar trend was observed for liver and kidney function biomarkers. Mechanistic studies revealed that @Calmat treatment activates the Bax/Bcl-2 signaling pathway, leading to cell cycle arrest in the G1 phase and subsequent late-phase apoptosis. As a result, the tumor inhibition rate reached 88%, with 80% of treated rats surviving beyond 100 days. These findings highlight the strong potential of @Calmat as a dual-function theranostic agent for the management of TNBC. © 2025 American Chemical Society.PublicationArticle 2-(Diarylalkyl)aminobenzothiazole derivatives induce autophagy and apoptotic death through SIRT inhibition and P53 activation In MCF7 breast cancer cells(Elsevier Ltd, 2025) Venkateswarlu Kojja; Dinesh Srinivas Kumar; Praveen Kumar Kalavagunta; Bhima Bhukya; Anjana Devi Tangutur; Prasanta Kumar NayakSirtuins (SIRTs) are multifunctional proteins that exhibit a wide range of substrate preferences and cellular localizations. They are reliant on NAD+ and are essential for the regulation of several cellular functions. The SIRT proteins play important role towards tumor survival and resistance mechanisms in tumor cells. Therefore, molecules targeting SIRT proteins gained significant recognition in cancer research. In this work, we explored the anticancer property, potential and mode of action of 2-(diarylalkyl)aminobenzothiazole derivatives on MCF7 human breast cancer cells. Our studies established that 2-(diarylalkyl)aminobenzothiazole derivatives 1-((6-chlorobenzo[d]thiazol-2-ylamino)(3,4-dichlorophenyl)methyl)naphthalen-2-ol (7ab) and 1-((6-chlorobenzo[d]thiazol-2-ylamino)(4-bromophenyl)methyl)naphthalen-2-ol (7ba) treatment in a dose dependent manner drastically lowered the cell proliferation in MCF7 cells and the IC50 values of 7ab and 7ba was found to be 11.4 µM and 9.6 µM at 24 hr in these cells. Docking and molecular dynamic simulation studies further revealed that 7ab and 7ba show significant binding with SIRT1 protein. Consistently, treatment with 7ab and 7ba reduced the expression levels of SIRT1 protein while increasing acetylation of p53, a known SIRT protein target in MCF-7 cells. We observed that SIRT1inhibition was associated with activation of p53, an essential protein for apoptotic cell death, in MCF-7 cell lines. Furthermore, 7ab and 7ba treatment induced LC3-II expression and vacuole formation in the cytoplasm leading to autophagic cell death. Our findings together reveal the plausible cellular targets and specificity of these new small molecules as SIRT inhibitors, which increase p53 acetylation and suppress the proliferation of MCF-7 human breast cancer cells by triggering autophagic and apoptotic cell death. © 2025 Elsevier LtdPublicationArticle Heteroaryl-Capped Hydroxamic Acid Derivatives with Varied Linkers: Synthesis and Anticancer Evaluation with Various Apoptosis Analyses in Breast Cancer Cells, Including Docking, Simulation, DFT, and ADMET Studies(Multidisciplinary Digital Publishing Institute (MDPI), 2025) Ekta Shirbhate; Biplob Koch; Vaibhav Singh; Akanksha Dubey; Haya Khader Ahmad Yasin; H. RajakBackground/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI50 < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC50 of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. © 2025 by the authors.PublicationArticle hsa-miR-22-3p-Mediated Exosome Release From Neurons Induces Apoptosis in Recipient Glial and Neuronal Cells in Parkinson's Disease Stress Conditions(John Wiley and Sons Inc, 2025) Shatakshi Shukla; Shanikumar Goyani; Dipanwita Chakraborty; M. V. Saranga; Minal Mane; Nisha Chandak; Jyoti Singh; Fatema Currim; Anjali Shinde; Sumedha Shah; Shyam Kishore; Bhumika Wadhwa; Sharad Gupta; Rajesh Kumar SinghExosome-mediated intercellular communication between different cell types and brain regions is essential for the homeostasis of the nervous system and any dysfunctions lead to the progression of several neurodegenerative disorders including Parkinson's disease (PD). Exosome biogenesis and release from the specific cell types are modulated by interorganellar crosstalk, and the transfer of exosomal cargo influences the functional outcome in the recipient cells. The miRNA–mRNA interaction modulates mRNA translation and stability; yet the understanding of specific miRNAs modulating exosome release in neuronal cells during PD stress is not well characterized. Bioinformatics analysis of different databases identified the putative mRNA targets for hsa-miR-22-3p suggesting its regulatory role in pathways of exosome release, autophagy and apoptosis. hsa-miR-22-3p levels were downregulated in neuronal SH-SY5Y cells under PD stress conditions induced by 6-OHDA and rotenone. hsa-miR-22-3p expression downregulates LAMP1, BCL2 and p62 protein levels in neuronal cells, impairing autophagic flux and mitochondrial-lysosomal functions, enhancing exosome release. Exosomes derived from hsa-miR-22-3p-expressing neuronal cells were actively internalized by glial and neuronal cells, exhibiting distinctive morphological features and cell death. The present study highlights the role of hsa-miR-22-3p in modulating the interorganelle communication, influencing exosome release and exacerbating neuronal and glial cell death during PD stress conditions. © 2025 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.PublicationArticle Investigations on Antiproliferative Potential of Thiosemicarbazone Zn(II) Complexes: Design, Synthesis, and Density Functional Theory Studies on Structural Parameters(John Wiley and Sons Ltd, 2025) Shivendra Kumar Pandey; Abhishek Kumar; Sushil Kumar Gupta; Ajay Vinod Kumar; Manoj Kumar BhartyZinc complexes have promising possibilities as medicines since they have better efficacy and lower toxicity. Herein, two ligands are synthesized based on hydrazine-1-carbothioamide with substituents having different electronic nature {nitro (HNPhHCT) and methoxy (HMoPhHCT)} and their respective Zn(II) complexes {[Zn(NPhHCT)2] and [Zn(MoPhHCT)2]}. They have been fully characterized via several spectroscopic techniques (IR, NMR, HRMS, UV–Vis studies) and DFT studies. In addition, ligands and their respective complexes are screened for their antiproliferative activity against three different cancer cell lines, namely HuT-78 (T-cell lymphoma), DL (Dalton's lymphoma), and MCF-7 (Breast cancer) cell lines. Among the two complexes, [Zn(MoPhHCT)2] is found to be most cytotoxic on all three cancer cell lines. In HuT-78 cells, [Zn(MoPhHCT)2] exhibited IC50 value at ≈4 µM. Further, glucose and ROS estimation assays suggested that [Zn(MoPhHCT)2] shows antiproliferative activity against T lymphoma cells by inhibiting their glycolytic activity and apoptosis induction by increasing ROS production. A molecular docking study is performed against an antiapoptotic protein, BCL2 (PDB: 2O2F), that confirms its inhibitory response with a binding score of −8.34 kcal mol−1. Further, the expression of BCL2 at the protein level is found to be significantly inhibited in response to treatment with [Zn(MoPhHCT)2], as evident by the Western blot analysis results. © 2025 Wiley-VCH GmbH.