Browsing by Author "Arbind Acharya"

Now showing 1 - 20 of 57

A benzophenanthridine alkaloid, chelerythrine induces apoptosis in vitro in a Dalton′s lymphoma
(2013) Sanjay Kumar; Praveen Deepak; Pramod Gautam; Arbind Acharya
Purpose: The aim of this study was to investigate the effect of chelerythrine on DL cell apoptosis in an in vitro experimental setup. Materials and Methods: For tumor model, spontaneous occurring T-cell lymphoma designated as Dalton′s lymphoma (DL) was selected. Double staining, transmission electron microscope (TEM), fluorescence microscopy, Western blotting, Reverse Transcriptase-Polymerase Chain Reaction, and DNA fragmentation assay were used to detect heat shock factor 1 (HSF1) and hsp70 expression and PKC phosphorylation, and apoptotic characteristic of DL cells. Results: Chelerythrine exposure resulted in significant morphological alteration comparable to that of apoptosis. Furthermore, it was confirmed by fluorescence microscopy, TEM analysis, and DNA fragmentation assay that 10 g/mL of chelerythrine is capable of inducing apoptosis in DL cells. The suppression in HSF1 expression and subsequent inhibition of hsp70 expression in chelerythrine-treated DL cells suggest that chelerythrine induces apoptosis in DL cells by inhibiting the expression of these cytoprotective proteins. Conclusion: Chelerythrine is capable of inducing apoptosis DL cells in vitro and therefore, it could be useful in combating tumor growth and progression.
Achyranthes aspera L. leaf extract induced anticancer effects on Dalton's Lymphoma via regulation of PKCα signaling pathway and mitochondrial apoptosis
(Elsevier Ireland Ltd, 2021) Rishi Kant Singh; Praveen Kumar Verma; Amit Kumar; Sandeep Kumar; Arbind Acharya
Ethnopharmacological relevance: Epidemiological studies promote the inclusion of natural-products in diet due to their inhibitory effects on various types of cancer. Among them, Achyranthes aspera L. (Family Amaranthaceae) is a medicinal plant in Ayurvedic pharmacopeia, found in India, Southeast Asia, America, and Sub-Saharan Africa. It is endowed with anti-inflammatory, anti-oxidant, and anti-cancer activities. However, its potential effect on Non-Hodgkin lymphomas (NHLs), has not yet been clarified. Aim of the study: In the present study, we aimed to investigate the effect of Achyranthes aspera L. leaf extracts on highly aggressive murine NHL called Dalton's Lymphoma (DL) in vitro and in vivo. Material and methods: GC-HRMS analysis was carried out for the identification of compounds present in A. aspera leaf extract. The cytotoxicity of various A. aspera leaf extracts was evaluated on DL cells by MTT assay. Chromatin condensation, nuclear fragmentation, and morphological changes were observed by microscopy technique. Flow cytometry was used to measure the changes in mitochondrial membrane potential (ΔΨm) and apoptosis. In addition, the expressions of apoptosis-related proteins were detected by western blotting. Meanwhile, the in vivo anti-tumor effect of leaf extract was tested in DL induced Balb/c mice. Result: GC-HRMS analysis of A. aspera methanolic leaf extract (AAML) revealed the presence of ten pharmacologically active compounds. The results showed that AAML suppressed cell proliferation, decreased mitochondrial membrane potential, changed the morphological structure, and induced apoptosis. Moreover, AAML could promote the release of cytochrome c by regulating Bcl-2 family proteins and then activated caspase-9/ -3 to triggered cell apoptosis. At the same time in DL cells treated with AAML, the protein kinase Cα (PKCα) pathway was inhibited in a concentration-dependent manner. Remarkably, in vivo, AAML mediated suppression of DL growth in Balb/c mice was accompanied by attenuation of the PKCα pathway and induction of apoptosis. Our result suggested that AAML promotes mitochondrial apoptotic cascade in DL cells by suppressing the PKCα signaling pathway. Conclusion: The study suggests that AAML could potently suppress DL progression by promoting apoptosis via mitochondrial-cascade and attenuation of the PKCα signaling pathway. © 2021
Activation of p53-dependent/-independent pathways of apoptotic cell death by chelerythrine in a murine T cell lymphoma
(Informa Healthcare, 2015) Sanjay Kumar; Munendra Singh Tomar; Arbind Acharya
The p53 tumor suppressor protein has been implicated as an activator of apoptosis. In order to investigate the effect of chelerythrine and staurosporine on the activation of p53-dependent/-independent pathways of Dalton lymphoma (DL) cell death, cells were treated with chelerythrine and staurosporine for 1 h, 3 h and 6 h, respectively. It was found that treatment with chelerythrine and staurosporine increased the expression of total-p53/phospho-53 (ser-15) significantly at protein and mRNA levels, which resulted in activation of the p53-dependent apoptotic pathway in DL cells. In addition, increased activities of cyt-c, caspase-9 and caspase-3 and degradation of DNA into fragments confirmed activation of the p53-independent apoptotic pathway in p53 knockdown RNAi-DL cells. In brief, the present study demonstrated activation of p53-dependent/-independent apoptotic pathways in DL cells. Therefore, targeting of p53-dependent/-independent apoptotic pathways may lead to the possibility of designing and developing better therapeutic regimens to treat DL and other human cancers. © 2015 Informa UK, Ltd.
Anti-tumor immunity and mechanism of immunosuppression mediated by tumor cells: Role of tumor-derived soluble factors and cytokines
(2010) Praveen Deepak; Arbind Acharya
The immune system plays a crucial role in the protection against tumor growth and progression. However, the activation of the immune system against the neoplastic cells does not always occur and, therefore, tumor cells are able to grow and progress continually in the host. It has now been realized that tumor cells themselves produce many of the important factors that are responsible for dismounting of effective immune response. These tumor-derived soluble factors invariably subdue the functions of almost every immune cell population. Therefore, we attempted to underline the mechanism of anti-tumor immune response and immunosuppression induced by tumor cells. © Copyright © 2010 Informa Healthcare USA, Inc.
Anticancer activity of Co(III) complex containing mixed ligand bis(5-phenyl-1,2,4-triazole)-3-sulfinamide and o-phen: Crystal structure, DFT, and Hirshfeld surface analysis
(Elsevier B.V., 2025) Shivendra Kumar Pandey; S. Dasaratha Kumar; Riya Kumari; Arbind Acharya; Ray Jay Butcher; Manoj Kumar Bharty
The cobalt complexes have demonstrated potential as antibacterial, antifungal, and anticancer agents, further enhancing their significance in the field of medicinal chemistry. Here, a cobalt(III) complex [Co(ptsm)H2O(o-phen)]·CH3OH containing in situ formed bis(5-phenyl-1,2,4-triazole)-3-sulfinamide (ptsm), 1,10-phenanthroline, and H2O molecule as ligand along with methanol molecule as crystallized solvent has been synthesized and characterized by various spectroscopic and X-ray crystallography techniques. The cobalt complex crystallizes in a triclinic system with space group P-1. The DFT and TD-DFT calculations were also performed to optimize geometry and better understand electronic transitions. The outcomes of quantum chemical calculations (TD-DFT and DFT) match the characteristics of the experiments. Various intermolecular interactions in complex 1 have been quantitively explained with Hirshfeld surface analysis. The MTT assay assessed the cytotoxicity of complex 1 against Dalton's lymphoma (DL) cells, yielding IC50 values of 40 µM. The AO/EtBr dual staining and DAPI staining further confirm the cytotoxic potential of the complex 1. © 2024 Elsevier B.V.
Anticancer evaluation of Co(III) complex derived from 1-isonicotinoyl-4-(4-nitrophenyl)-3-thiosemicarbazide: Structural characterization, photophysical, and Hirshfeld studies
(Elsevier B.V., 2025) Ram Nayan Gautam; Alok Shukla; Suryansh Chandra; Sundeep Kumar; Arbind Acharya; Mamata K. Singh; Ray Jay Butcher; Manoj Kumar Bharty
A new cationic complex, [Co((intph)(en)2]Cl, derived from the 1-isonicotinoyl-4-(4-nitrophenyl)-3-thiosemicarbazide (H2intph), is reported. The synthesized ligand and its corresponding Co(III) complex were successfully characterized by applying FT-IR and UV–visible spectroscopic techniques and single crystal ray diffraction data. Molecular geometries of the ligand and its Co(III) complex were accurately determined from their respective X-ray crystallographic analysis. The ligand and [Co((intph)(en)2]Cl crystallize in Triclinic and monoclinic systems with space groups P-1 and P 21/n, respectively. The crystal structures of H2intph and [Co((intph)(en)2]Cl are stabilized by weak C-H⋯O, N-H⋯O, and C-H⋯Cl hydrogen bonding interactions. Hirshfeld surface analysis was accomplished to investigate intermolecular hydrogen bonding interactions found in ligand H2intph and [Co((intph)(en)2]Cl. The cytotoxicity of the ligand and the complex [Co((intph)(en)2]Cl was assessed for their anticancer potential against human glioblastoma (U87) and Dalton lymphoma (DL) cell lines. The complex exhibited IC50 values of 100 μg/mL for U87 cells and 120 μg/mL for DL cells, indicating the concentration at which 50 % of cell viability was inhibited. In comparison, the ligand was less effective in the MTT assay against both U87 and DL cells. These results suggest that the complex [Co((intph)(en)2]Cl significantly reduces glioblastoma cell viability. Treatment with the complex induced cell death through both apoptotic and necrotic pathways, as evidenced by Hoechst/PI double staining. Additionally, there was an increase in intracellular reactive oxygen species (ROS), highlighting the role of oxidative stress in the anticancer activity of the [Co((intph)(en)2]Cl complex. Furthermore, fluorescence studies were carried out which revealed the order of fluorescence behaviors between the ligand and the Co(III) complex to be Co(III) complex > H2intph. © 2024 Elsevier B.V.
Antigenic Hsp70–peptide upregulate altered cell surface MHC class I expression in TAMs and increases anti-tumor function in Dalton’s lymphoma bearing mice
(Kluwer Academic Publishers, 2015) Pramod Kumar Gautam; Arbind Acharya
Major histocompatibility complex (MHC) class I molecules not only provide a mechanistic framework for the cell-to-cell communication, but also possess broader biological function. Due to their ability to regulate presentation of tumor-associated antigens (TAAs), viral peptides which play an essential role in the regulation of immune responses by presenting antigenic peptides to cytotoxic T lymphocytes and by regulating cytolytic activities of immune cells. Tumor cells frequently do not express MHC class I molecules; as a result, tumor cells escape from immune surveillance. Cells surviving in tumor microenvironment are often characterized by a profound immune escape phenotype with alterations in MHC class I way of antigen processing. Cellular components of the tumor microenvironment, in particular alternatively activated M2 phenotype, are involved in tumor progression and suppression of anti-tumor immunity. Hsp70 is well recognized for its role in activating macrophages leading to enhanced production of inflammatory cytokines. It has been observed that Hsp70 derived from normal tissues do not elicit tumor immunity, while Hsp70 preparation from tumor cell associated with antigen are able to elicit tumor immunity. The finding shows that the expression of MHC class I (H2Db) drastically decreases in TAMs and Hsp70–peptide complex enhances H2Db expression in TAMs and it reverts back the suppressed function of TAMs into the M1 state of immunoregulatory phenotype that promotes tumor regression by enhanced antigen presentation. © 2014, International Society of Oncology and BioMarkers (ISOBM).
Autologous Hsp70 induces antigen specific Th1 immune responses in a murine T-Cell lymphoma
(2009) Sanjay Kumar; Praveen Deepak; Sanjay Kumar Jr.; Dhiraj Kishore; Arbind Acharya
Heat Shock protein-70 derived from tumor cells is highly immunogenic and induces specific anti-tumor immune response by directly activating cytotoxic CD8+ T cells. Additionally, Hsp70 is known to be a strong activator of antigen presenting cells and therefore, up regulates the production of pro-inflammatory cytokines and chemokines. In this study, we have shown the effect of tumor-derived Hsp70 on the induction of delayed type hypersensitivity reaction in a T cell lymphoma bearing mice. The autologous Hsp70 augments contact hypersensitivity and delayed type hypersensitivity responses in mice challenged with allergen in vehicle and antigens respectively. The adoptive transfer of splenocytes derived from Hsp70 immunized mice is able to enhance delayed type hypersensitivity response in antigen challenged normal and DL-bearing host. Furthermore, adoptive transfer of macrophages incubated with autologous Hsp70 also enhances DTH reactivity in mice. The pro-inflammatory cytokines and C-C chemokines are found to be elevated in the DTH footpad extract of antigen challenged normal and DL-bearing mice. Increased production of IFN-γ and MIP-1α± suggest that autologous Hsp70 augments the recruitment of antigen specific Th1 cells, which further secretes pro-inflammatory cytokines and C-C chemokines mediating the hypersensitivity reaction upon challenge with antigens. © 2009 Informa Healthcare USA, Inc.
Biological functions of IL-4/IL-13, signaling cascades and implication in growth and development of tumor
(Nova Science Publishers, Inc., 2012) Praveen Deepak; Arbind Acharya
Interleukin-4 and 13 are immunoregulatory cytokines secreted mainly by activated Th2 cells. They regulate multiple biological functions such as proliferation, differentiation and apoptosis in various cell types of hematopoietic and non-hematopoietic origin. Both cytokines are critical to the differentiation of Th0 cells into Th2 cells and simultaneous suppression of Th1 type T cell-mediated immunity thus involved in the amplification of Th2 type of immune responses. Acting on the every immune cell population through their cell surface receptors, they are able to subdue the antitumor function of immunopotent cells and tumor immunosurveillance mechanism(s), and therefore favor unrestricted growth and progression of tumor. Both cytokines have shared biological effects due to common receptor subunits. They have both type I and type II receptor complexes forming at least four receptor complexes viz IL-4Rα-γc, IL-4Rα-IL-13Rα1, IL-4Rα-IL-13Ra2, IL-13Ra2 expressed in many tumor cell types. IL-4 and IL-13 mediate signal through two different pathways IL-4-IRS pathway involving insulin receptor substrate molecules leading to the activation of MAPK and PKC and JAK-STAT pathway resulting in the activation of STAT6. MAPK and PKC activated in response to IL-4 and IL-13 leads to tumor cell growth and survival by activating proliferation and anti-apoptotic mechanism(s), while STAT6 activation leads to the expression of CD23, MHC class II, germ line immunoglobulin ε, CD45, SOCS etc. In addition, signaling through IL-13Ra1 leads to activation of several STAT molecules including STAT1α, 3, 5α, 5β and STAT6, all results in the proliferation of tumor cells and differentiation of Th2 cells. IL-13Rα2, previously known as decoy receptor, also transduce signal and leads to the activation of ERK and p38 MAPK which regulate proliferation and metastasis of tumor cells. The signaling cascades induced by IL-4 and IL-13 are modulated by many adaptor and regulatory molecules, which are also known to be associated with many hematological and non-hematological malignancies and therefore they could be an attractive target to develop a therapeutic agent for the treatment of cancer. © 2013 by Nova Science Publishers, Inc. All rights reserved.
Carboxylic group-induced synthesis and characterization of selenium nanoparticles and its anti-tumor potential on Dalton's lymphoma cells
(Elsevier B.V., 2015) Sanjay Kumar; Munendra Singh Tomar; Arbind Acharya
Carboxylic group-induced synthesis of selenium nanoparticles (SeNPs) was achieved using sodium selenosulphate as a precursor. The particles were stabilized and capped with 0.01% polyvinyl alcohol under ambient conditions. This is a simple and easy method of producing SeNPs in a size range from 35 to 105. nm. The synthesized SeNPs were purified by centrifugation at 11,500. ×. g for 20. min and characterized by UV-visible spectroscopy, FTIR spectroscopy, XRD, DSC and TEM. It was observed that the synthesized SeNPs showed differences in their absorption spectra, phase composition and crystal structure, thermodynamic behaviour, size and shape. Further, to confirm anti-tumour potential of the synthesized SeNPs induced by the carboxylic group of acetic acid, pyruvic acid and benzoic acid, cell viability assay, nuclear morphology testing and DNA fragmentation assay were carried out using Dalton's lymphoma (DL) cells. DL cells treated with the SeNPs showed reduced cell viability, altered nuclear morphology, typical apoptotic DNA ladder and apoptosis. Therefore, these SeNPs may have therapeutic relevance to treat this type of cancer. © 2015 Elsevier B.V.
CD28-mediated T cell response is upregulated by exogenous application of autologous Hsp70–peptide complex in a tumor-bearing host
(Humana Press Inc., 2016) Sanjay Kumar; Pramod Kumar Gautam; Munendra Singh Tomar; Arbind Acharya
Hsp70, a highly conserved protein, has gained plenty of attention by virtue of its adjuvant capability to induce peptide-specific cytotoxic T lymphocyte responses. In this study, we have investigated the effect of autologous Hsp70–peptide complex (or simply autologous Hsp70) on the expression of CD28 on T cells and its effector functions through macrophage activation. Further, we investigated the effect of Hsp70 on the expression of CD80 and CD86 on macrophages isolated from normal and tumor-bearing host to provide costimulatory signal for T cell activation and secretion of IL-2 and IFN-γ during interaction. We found that treatment of autologous Hsp70 effectively activated TAMs to induce higher expression of CD28 on T cells through T cells–macrophage interaction. Treatment of autologous Hsp70 induces higher expression of CD80 and CD86 on TAMs, as a result, increases B7/CD28 interaction, which in turns activates T cells and induces higher production of IL-2 and IFN-γ, thereby increasing antigen-specific T cell proliferation. With our novel study, we have provided the strong insights into the role of extracellular Hsp70 on the expression of CD28 costimulatory molecule on T cells, which helps in the activation and generation of antigen-specific T cell effector functions in a tumor-bearing host to curb malignancy. © 2015, Springer Science+Business Media New York.
Chelerythrine delayed tumor growth and increased survival duration of Dalton's lymphoma bearing BALB/c H 2d mice by activation of NK cells in vivo
(Medknow Publications, 2015) Sanjay Kumar; Munendra Singh Tomar; Arbind Acharya
Aim: The aims of the present investigation were to evaluate the antitumor effect of chelerythrine (CHE) on in vivo growth and survival duration of BALB/c (H 2d ) mice bearing Dalton's lymphoma (DL) and enhanced function of tumor associated NK cells (TANK cells). Materials and Methods: BALB/c (H 2d ) mice at 8-10 weeks of age of either sex were used. Increasing concentration of CHE (1.25, 2.5, and 5.0 mg/kg), staurosporine (0.625, 1.0, 1.5, and 2.0 mg/kg) and cyclophosphamide (25, 50, 100, and 200 mg/kg) were administered intraperitoneally and tumor regression and survival duration of tumor bearing host were determined, and thereafter expression of NKG2D and NKG2A on TANK cells were detected. Results: Our results show that treatment with 2.5 mg/kg of CHE results in a significant reduction in mean tumor volume and increased survival duration of DL bearing BALB/c (H 2d ) mice when compared to control. Activating receptor NKG2D on TANK cells were observed upregulated in contrast to inhibitory receptor NKG2A. Conclusions: CHE reduced mean tumor volume and increased survival duration of DL bearing BALB/c (H 2d ) mice. Increased expression of activating receptor NKG2D on TANK cells results in recovery of immunosuppression during tumor progression. Therefore, CHE could be a potential anticancer therapeutic agent that may be used to replace chemo-radio-therapy in future. © 2015 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.
Chelerythrine induces reactive oxygen species-dependent mitochondrial apoptotic pathway in a murine T cell lymphoma
(IOS Press BV, 2014) Sanjay Kumar; Arbind Acharya
Chelerythrine is a well-known protein kinase C inhibitor and potential antiproliferative and antitumor pharmacological agent. Chelerythrine inhibits/suppresses the HSF1 phosphorylation by inhibiting PKC and blocks the nuclear migration and subsequent synthesis of hsp70 leading to reduced cell viability and activation of apoptotic machinery. Chelerythrine is also known to enhance the production of reactive oxygen intermediate that is strong activator of apoptosis in high concentration. Therefore, the present study intended to investigate the role of chelerythrine-induced reactive oxygen intermediate on the viability and apoptosis of Dalton's lymphoma cells. Enhanced production of reactive oxygen species in Dalton's lymphoma (DL) cells was observed upon treatment of chelerythrine only which was seen completely abolished on treatment of mitochondrial complex inhibitors rotenone and malonate, and anti-oxidant, N-acetyl-l-cysteine. Increased number of DL cells undergoing apoptosis, as observed by fluorescent microscopy and flow cytometry analysis, in chelerythrine only-treated group was seen that was significantly inhibited on treatment of mitochondrial complex inhibitors and anti-oxidants. Staurosporine, on the other hand, does not lead to enhanced production of reactive oxygen intermediate in DL cells. © 2013 International Society of Oncology and BioMarkers (ISOBM).
Chitosan-based self-healing hydrogel mediated by poly(acrylic-methacrylic acid) exhibiting high biocompatibility and anti-tumor activity
(John Wiley and Sons Inc, 2024) Krishtan Pal; Sandeep Kumar; Paramjeet Yadav; Sheetal Jaiswal; Rajesh Kumar; Arbind Acharya
Multi-responsive, self-healing hydrogels were developed utilizing positively charged polysaccharides, chitosan, and water-soluble chitosan. This fabrication employed free-radical synthesized polyacrylic acid and polymethacrylic acid along with the cross-linker FeCl3, resulting in the generation of polyelectrolyte metal complexes, which enhances the properties of the chitosan-based hydrogels, particularly their mechanical strength, self-healing ability, thermal stability, swelling behavior, porous structure, cell viability, and even anticancer activity. Characterization and stability assessment of the hydrogels were performed using FT-IR, nuclear magnetic resonance, gel permeation chromatography, scanning electron microscopy, rheometer, x-ray diffraction, thermogravimetric analysis, DSC, and UV spectroscopy. FT-IR measurements indicated that the facile complexation of the cross-linker's metal ions (Fe3+) with the carboxylate (COO−), amino (NH), and hydroxyl (OH) groups of the polymers and chitosan chains facilitated rapid gelation. Furthermore, the sustained release of the drug levofloxacin (up to 80%) was observed to increase with increasing pH due to the hydrogels' anionic nature. Biocompatibility and cytotoxicity tests were conducted using the MTT assay on splenocytes and Dalton Lymphoma cancer cell lines. These tests demonstrated the promising potential of these hydrogels for drug delivery applications. © 2024 Wiley Periodicals LLC.
Cobalt (III) complex exerts anti-cancer effects on T cell lymphoma through induction of cell cycle arrest and promotion of apoptosis
(Springer Science and Business Media Deutschland GmbH, 2022) Praveen Kumar Verma; Rishi Kant Singh; Sandeep Kumar; Alok Shukla; Sanjay Kumar; Mannu Kumar Gond; Manoj Kumar Bharty; Arbind Acharya
Purpose: Cobalt-based compounds are emerging as a non-platinum-based anti-cancer effective therapeutic agent. However, there is a limited study regarding the therapeutic efficacy of Cobalt-based drugs against Non-Hodgkin’s Lymphoma (NHLs) such as T cell lymphoma. Therefore, in the present study we investigated the anti-tumor role of cobalt(III) complex [Co(ptsm)NH3(o-phen)]·CH3OH on Dalton’s Lymphoma (DL) cells. Materials and methods: Cytotoxicity of the cobalt complex was estimated by MTT assay. Analysis of mitochondrial membrane potential, cell cycle and Reactive oxygen species (ROS) generation, and Annexin V/PI staining was done by Flow cytometry, while AO/EtBr staining by fluorescence microscopy in cobalt complex treated DL cell. Expression of cell cycle and apoptosis regulatory protein was analyzed by Western blotting. In addition, in vivo study of the cobalt complex was evaluated in well-established DL bearing mice by monitoring physiological parameters and mean survival time. Results: Our study showed that cobalt complex triggered apoptosis and induced cell cycle arrest in DL cells. Furthermore, this also decreased mitochondrial membrane potential and increased intracellular ROS generation in cancer cells. In addition, changed expression of cell cycle and apoptosis regulatory protein was found with enhanced activity of caspase-3 and 9 in the treated cells. Additionally, administration of cobalt complex showed a significant increase in the survivability of tumor-bearing host, which was accomplished by decreasing physiological parameters. Conclusion: Taken together, these data revealed anti-tumor potential of cobalt complex against DL cells through cell cycle arrest and mitochondrial-dependent apoptosis. Henceforth, cobalt-based drugs could be a new generation therapeutic drug to treat hematological malignancies. Graphical abstract: [Figure not available: see fulltext.]. © 2022, Springer Nature Switzerland AG.
Comprehensive property combination for biomedical application achieved in a Ti35Zr35Nb15Mo5Fe5Cr5 complex concentrated alloy
(Elsevier Ltd, 2024) Dharmendra K. Yadav; Anand K. Patel; Shruti R. Hansda; Arbind Acharya; Lakhindra Marandi; Surya D. Yadav; Subhasis Sinha
A novel Ti35Zr35Nb15Mo5Fe5Cr5 complex concentrated alloy (CCA) with potential for biomedical application was developed by vacuum arc melting and its microstructural evolution, mechanical properties, corrosion and wear behavior, and cytocompatibility were systematically evaluated. The alloy has an experimentally measured density of 6.37 g/cm³, suitable to fulfill the requirement of light weight. XRD analysis revealed that the as-cast and annealed specimens contain two BCC solid solution phases and a TiCr2 type Laves phase. The average microhardness (H) and elastic modulus (E) of the as-cast CCA are 618.39 ± 9.26 HV and 97.32 ± 3.58 GPa, respectively. Moreover, the yield strength (YS) of the as-cast alloy, estimated from elastoplastic analysis of the microindentation data, is 1203.94 ± 30.28 MPa. However, the CCA annealed at 1100˚C exhibits a microhardness of 833.08 ± 7.58 HV and a YS of 1669.65 ± 24.79 MPa, with the elastoplastic stress-strain response revealing no significant loss of plasticity due to the increased hard Laves phase. Corrosion and wear tests conducted in simulated body fluid confirmed the alloy's excellent corrosion and wear resistance. Cell culture experiments with MG-63 and HEK-293 cells demonstrated superior cell viability and proliferation compared to CP-Ti and 316 L SS. Moreover, confocal fluorescence images of MG-63 cells stained with AO/EtBr, Rh-123, and DCFH-DA revealed that the present CCA exhibits good biocompatibility. Thus, a comprehensive combination of low density, compatible elastic modulus, good strength with adequate plasticity, and sufficient corrosion resistance and biocompatibility were successfully achieved, unraveling significant potential of the alloy for biomedical applications. © 2024 Elsevier Ltd
Developing a nontoxic and biocompatible polymeric self-assembly by using RAFT methodology for biomedical application
(Elsevier Ltd, 2019) Deepak; Swati Sharma; Ashok Kumar; Rajesh Kumar; Koushik Nandy; Arti Srivastava; Munendra Singh Tomar; Arbind Acharya
The amphiphilic block copolymer poly(N-vinylpyrrolidone)-b-poly(N-vinylcarbazole) (PVP-b-PVK) was synthesized by reversible-deactivation radical polymerization (RDRP)using reversible addition-fragmentation chain transfer (RAFT) methodology by new chain transfer agent (CTA) i.e. benzyl piperidine dithiocarbamate (BPDC). The pseudo-first-order kinetics and linear evolution of the molar mass with N-vinylpyrrolidone (NVP) conversion were obtained with the molar mass dispersity (Ð) 1.30–1.41 in toluene. 1H NMR spectrum indicates the presence of chain-end functional groups on homopolymer and block copolymer. The above block copolymer get self-assembled and form micelles in the aqueous medium, the size of micelles is characterized by 1H NMR, transmission electron micrographs (TEM) and dynamic laser light scattering (DLS) analyses, and critical micelles concentration (CMC) was determined by UV–vis spectroscopy. Trypan blue exclusion and MTT assay were done to ensure the cytotoxic effect of PVP-b-PVK on different types of normal cells (thymocytes, splenocytes and macrophage), and no cytotoxic effect was shown by block copolymer on cells, while observed biocompatibility with cells was 200 mg/mL. Further, the beads of block copolymer releases (65%) highly water-soluble levofloxacin drug up to 8 h in a controlled manner at pH 7.4 (37 ± 0.2 °C), while loading of levofloxacin drug was 62% (w/w). © 2018 Elsevier Ltd
Evidence that PKCα inhibition in Dalton's Lymphoma cells augments cell cycle arrest and mitochondrial-dependent apoptosis
(Elsevier Ltd, 2022) Rishi Kant Singh; Praveen Kumar Verma; Sandeep Kumar; Alok Shukla; Naveen Kumar; Sanjay Kumar; Arbind Acharya
Protein kinase Cα (PKCα), belonging to ser/thr protein kinase, perform various biological functions. Overexpression of PKCα has been observed in multiple human malignancies including lymphoma. However, the molecular pathogenesis and involvement of PKCα in Non-Hodgkin lymphoma (NHL) are not clearly understood. Hence, deciphering the role of PKCα in NHL management may provide a better therapeutic option. In the present study, we used selective pharmacological inhibitors Gö6976 and Ro320432 that potentially inhibit PKCα-mediated signaling in DL cells, resulting in the inhibition of cell growth and mitochondrial-dependent apoptosis. PKCα inhibition by these inhibitors also displays cell cycle arrest at the G1 phase and causes growth retardation of DL cells. Our results extended the mechanism of PKCα in NHL, and provided potential implications for its therapy. © 2022 Elsevier Ltd
Exploring the anticancer activity of 1-(2-methyl-3-furoyl)-4-phenyl-3-thiosemicarbazide and its Mn(II) complex: Synthesis, spectral, crystal structures, and Hirshfeld surface analysis
(Elsevier B.V., 2025) Rahul Chaurasia; Alok Shukla; Shivendra Kumar Pandey; Seema Gupta; Nishant Shekhar; Arbind Acharya; Ray Jay Butcher; Manoj Kumar Bharty
The chemistry of mixed ligand transition metal complexes has been of interest of researchers owing to its diverse application and bonding features. Herein, a new thiosemicarbazide derivative namely 1-(2-methyl-3-furoyl)-4-phenyl-3-thiosemicarbazide (HmfpTSC) has been synthesized along with its [Mn(mfpTSC)2(o-phen)] (C1) complex. The prepared ligand (HmfpTSC) and the complex have been confirmed via spectroscopic and single-crystal X-ray data. The HmfpTSC and complex crystallize in a monoclinic crystal system with space group P21/c and P21/n, respectively. HmfpTSC behaves as a uninegative bidentate ligand and its two-unit binds with metal ion along with one unit of o-phen. Using Hirshfeld surface analysis, the weak interactions seen in HmfpTSC and complex have been quantitatively investigated. The MTT assay was used to assess the cytotoxicity of HmfpTSC and [Mn(mfpTSC)2(o-phen)] complex against Dalton's lymphoma cells. Further, the mechanism of anticancer action of ligand and complex was investigated through DAPI, AO/EB staining, and flow cytometry. The both AO/EB and DAPI staining provided compelling evidence of complex-induced cellular and nuclear changes consistent with apoptosis and necrosis. © 2024
Exploring the synthesis, characterization, crystal structures, DFT calculation, hirshfeld surface analysis, and anticancer activity of Ni(II) complex of 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide
(Elsevier B.V., 2025) Shivendra Kumar Pandey; Rahul Chaurasia; Alok Shukla; Riya Kumari; Nishant Shekhar; Arti Srivastava; Arbind Acharya; Ray Jay Butcher; Manoj Kumar Bharty
The chemistry of biologically active thiosemicarbazide has been of interest to researchers owing to its diverse application and bonding features. In the present study, a new thiosemicarbazide derivative namely 1-(4-nitrobenzoyl)-4-phenyl-3-thiosemicarbazide (HnbphTSC) has been prepared and along with its [Ni(nbphTSC)2(en)]·CHCl3 (1) complex. The prepared ligand (HnbphTSC) and complex 1 have been characterized through spectroscopic and single-crystal X-ray data. The HnbphTSC and complex 1 crystallize in triclinic and monoclinic crystal systems with space groups P1¯ and P21/C, respectively. The weak interactions present in HnbphTSC and complex 1 have been quantitively studied through hirshfeld surface analysis. The physiochemical characteristics of HnbphTSC and complex 1 are also verified using DFT calculations, and the resultant results are in strong agreement with the experimental findings. The HOMO and LUMO energy gap have been calculated as 3.160 eV and 2.212 eV for HnbphTSC and complex 1, respectively. MTT assay was used to evaluate the cytotoxicity of HnbphTSC and complex 1 against Dalton's lymphoma (DL) cells. We further assessed the mode of tumor cell death and the drug's effect on nuclear condensation and plasma membrane integrity by employing DAPI/PI dual staining technique. © 2024 Elsevier B.V.