Browsing by Author "A. Acharya"

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Autologous Hsp70 immunization induces anti-tumor immunity and increases longevity and survival of tumor-bearing mice
(SAP - Slovak Academic Press, spol. s.r.o., 2009) S. Kumar; P. Deepak; A. Acharya
Heat Shock proteins 70 (Hsp70) is a family of highly conserved molecules that maintain the function of crucial cellular pathways during stress. Hsp70 derived from tumor cells is bound with tumor antigenic peptides from the diverse antigen cytosolic pool. Tumor-derived Hsp70 preparations after ex vivo administration permit antigen presenting cells (APCs) to present tumor antigen to their cell surface and induce tumor specific immunity in many types of malignancies by directly eliciting cytotoxic T-lymphocytes (CTL) response. In the present investigation, we have demonstrated that immunization with tumor cell derived Hsp70 lead to an effective survival advantage in mice with minimal residual tumor cells from which Hsp70 is derived, by involvement of immune cell types in the rejection of tumor in the Hsp70 immunized tumor-bearing host mice and their post-immunization cytokine repertoire. It has been observed that autologous Hsp70 induces specific anti-tumor immunity and effectively eradicates tumors in the host mice, thereby enhancing survival of tumor-bearing host. Immunization with tumor-derived autologous Hsp70 effectively primed specific CTL response and increased tumor cell lysis independently of CD4+ T-lymphocytes. Increase in type I cytokines in the serum of Hsp70 immunized mice was also observed that indicates its adjuvant property in the host. Furthermore, Hsp70 immunized mice did not show any systemic disorder. Therefore, it could be assumed as safe and might be clinically useful for vaccination against malignant human tumors.
Classical Protein Kinase C: a novel kinase target in breast cancer
(Springer-Verlag Italia s.r.l., 2019) R.K. Singh; S. Kumar; M.S. Tomar; P.K. Verma; S.P. Singh; P.K. Gautam; A. Acharya
Classical protein kinase C (cPKC) enzymes are ser/thr protein kinases that have been an important factor in regulating a variety of cellular functions required for both in terms of health and disease. Therefore, precise control of cPKC-mediated signal is necessary for cellular homeostasis; however, their dysregulation leads to the development of several pathophysiological conditions including cancer. In cellular microenvironment, cPKC-mediated signaling is accompanied by multiple molecular mechanisms including phosphorylation, second messenger binding, and scaffold proteins. Functional cPKC interacts with a number of cellular proteins involved in the regulation of multiple biological functions such as cell growth, survival, migration, and adhesion. Further, the role of cPKC varies from cell to cell, substrate to substrate and, therefore, it is plausible to assume that the dysregulation of cPKC activity causes cellular transformation. Currently, there is no sufficient literature available to provide better understating to develop an effective therapeutic regimen to reverse pathophysiological condition caused by functionally dysregulated cPKC. Therefore, in the present review, we have focused on to provide a better and detail information on the various aspects of cPKC such as structure, mode of activation, regulation, and distinct cellular functions useful for the development of an effective therapeutic regimen against the breast cancer. © 2018, Federación de Sociedades Españolas de Oncología (FESEO).
Effect of TNFα on the induction of apoptosis in murine macrophage: Role of interleukin-1β converting enzime
(Biomedical Research Press s.a.s., 2001) A. Acharya; S.M. Singh
Tumor necrosis factor α (TNF α) is a cytokine that induces apoptosis in various cell types via its binding to TNF-receptors (TNF-R). Involvement of ICE-like protease in the induction of TNF-α mediated apoptosis in murine macrophage was investigated using ICE inhibitor YVAD-cmk (Tetrapeptide-Acetyl-Try-Val-Ala-Asp-Chloromethyl ketone). Macrophages treated with TNF showed a time dependent decrease in cell viability with a simultaneous increase in the % of cells showing apoptotic morphology and an increase in % DNA fragmentation, a quantitative measure of apoptosis. However, incubation of macrophage in medium containing TNF and YVAD-cmk had inhibitory effect on the TNF-induced apoptosis of macrophage. This finding suggests that ICE-like protease may be involved in the induction of apoptosis in macrophage by TNF-α.
Experimental, spectroscopic, and theoretical investigation on structural and anticancer activities of Schiff bases derived from isonicotinohydrazide
(Elsevier B.V., 2023) Seema Gupta; Shivendra Kumar Pandey; Sandeep Kumar; Ram Nayan Gautam; A.K. Patel; M.K. Bharty; D. Kushwaha; A. Acharya; R.J. Butcher
Isoniazid hydrazones are promising possibilities as medicines since they have preserved efficacy and are less toxic and resistant to resistance than parent Isoniazid (INH). Here, we have synthesized a series of Schiff bases (INH1–9) derived from a clinically approved antitubercular drug Isoniazid (INH). These synthesized ligands have been characterized by various spectroscopic techniques like IR, UV–vis., NMR, HRMS, etc. Moreover, single crystal of three derivatives viz. INH4, INH8, and INH9 has been determined and they crystallize in monoclinic crystal system. Hirshfeld surface analysis has been performed to ascertain intermolecular interactions present in these compounds. The molecular geometry optimization and vibrational analysis of these compounds were performed using density functional theory (DFT) studies utilizing B3LYP/6–31++G(d, p) basis set. The TD-DFT analysis was also performed to understand electronic transitions and the nature of FMO in these compounds. There was a good correlation found between theoretical and experimental values, thereby confirming the molecular structures of synthesized compounds. Molecular docking studies were performed to obtain more insights on potential anticancer activities of these compounds along with standard anticancer drugs 5-fluorouracil and Tamoxifen against MDM2 (4HG7) protein. The outcome revealed a significant binding affinity of these compounds with target protein even better than 5-fluorouracil and comparable to Tamoxifen. The compounds (INH4 and INH9) having the strongest binding affinity with the target protein are further experimentally evaluated for their in-vitro cytotoxic action on Dalton's lymphoma cells employing MTT assay, fluorescence microscopy, and flow cytometry. IC50 value (150 µg/ml) of this compound is equated with before-reported complexes/molecules/extracts and found it has better or comparable cytotoxicity. © 2023 Elsevier B.V.
Exploring 2-(benzylthio)-5-(4-nitrophenyl)-1,3,4-oxadiazole as antiproliferative agent: Synthesis, single crystal XRD, DFT, Hirshfeld surface analysis, in vitro antiproliferative activity and molecular docking analysis
(Elsevier B.V., 2024) Riya Kumari; Shivendra K. Pandey; A.K. Patel; D. Kushwaha; A. Acharya; M.K. Bharty
In this investigation, an oxadiazole derivative namely 2-(benzylthio)-5-(4-nitrophenyl)-1,3,4-oxadiazole (2-Btno) was synthesized. The study delves into the exploration of its anticancer efficacy against Dalton's lymphoma (DL) tumor cells, obtained from murine T-cell lymphoma. The compound 2-Btno has been characterized by elemental analysis, IR, UV–Vis., NMR, and single-crystal X-ray diffraction data. The compound 2-Btno crystallizes in a monoclinic system with space group P 21/n. The crystal structure is stabilized by weak C[sbnd]H···O and N[sbnd]H···N hydrogen bonding weak interactions, which are quantitively examined through Hirshfeld surface analysis. The DFT calculations are also performed to verify physiochemical properties of 2-Btno and the results obtained are in good agreement with the experimental results. The HOMO and LUMO energy gap of 3.402 eV for 2-Btno indicates good NLO properties. The cytotoxic activity of 2-Btno against Dalton's lymphoma cells was assessed through the MTT assay. The results indicated notable anticancer efficacy, with an IC50 value of 80 μg/mL. The mode of action of compound 2-Btno was examined through various assays, and the findings indicate that compound 2-Btno functions by downregulating mitochondrial membrane potential and upregulating the reactive oxygen species (ROS) production. Molecular docking study was conducted to establish the correlation between the cytotoxicity of the compound and its binding affinity within the active sites of crucial anti-cancer and anti-apoptotic target proteins MDM2 (PDB: 3JZK), Bcl-XL (PDB: 4QVX) and Bcl-2 (PDB: 6O0K). © 2024
Gender variation in interleukin-13 production: A possible mechanism of differential in vivo growth of a T-cell lymphoma
(2008) P. Deepak; S. Kumar; A. Acharya
Interleukin (IL)-13 is a TH2 type of cytokine that plays a crucial role in the pathophysiology of different type of infections, autoimmune diseases and malignancies. It has been shown to dampen the TH1 type of immune responses and favours tumour growth. In the present investigation, we have determined IL-13 level in serum and ascitic fluid in both the sexes of BALB/c strain of mice bearing a T-cell lymphoma of spontaneous origin, designated as Dalton's Lymphoma (DL). Further, we have studied the involvement of gender hormones on the IL-13 level and NKT-cell production of IL-13. It has been observed that there exists a gender variation or gender dimorphism in the IL-13 production. IL-13 level in serum is directly correlated with in vivo progressive growth of DL cells. We observed a tendency in female DL-bearing mice to have higher serum IL-13 level and faster growth of DL cells. This study, therefore, indicates that sex hormones are directly involved in the differential production of IL-13 that may be a factor responsible, at least in part, for the differential in vivo progressive growth of a T-cell lymphoma. © 2008 The Authors.
H2O2-induced apoptosis of thymocytes involves mobilization of divalent cations
(Biomedical Research Press s.a.s., 2002) A. Acharya
More than 90% of thymocytes undergo apoptosis while undergoing differentiation in the thymus. Although several factors act in concert to induce thymocyte apoptosis, it remains speculative if reactive oxygen intermediates produced by thymic macrophages may play a role in this process. The present investigation was carried out to determine if H2O2 is capable of inducing apoptosis of thymocytes in vitro. It was observed that H2O2 could induce apoptosis of thymocytes in vitro in a dose and time dependent manner. It was further found that H2O2-induced thymocyte apoptosis was dependent on the mobilization of divalent cations. The result of this study will help further in the understanding of the mechanism of H2O2-induced apoptosis.
Hsp70 induces Th1 polarization through tumor-associated macrophages in a T-cell lymphoma
(SAP - Slovak Academic Press, spol. s.r.o., 2007) S. Kumar; P. Deepak; A. Acharya
Tumor progression produces immunoregulatory phenotype of macrophages in tumor bearing host (TBH), that mediate immunosuppression through increased production of soluble factors. These factors obviously suppress the T-cell responsiveness and underproduction of Th1-polarizing cytokines. Here, we reported that in vitro treatment of TAMs with autologous Hsp70 purified from DL-bearing mice reverse back the tumor induced macrophage suppressor activity, suggesting that Hsp70 can restore TAMs production of Th1-polarizing cytokines. LPS stimulation failed to overcome tumor-induced dysregulation of IL-1, IL-12, IL-15 and IFN-γ production. In contrary, Hsp70 significantly enhanced IL12, IL-15, IL-1 and IFN-γ production by TAMs in vitro and in vivo, but also enhanced the LPS and IFN-γ responsiveness of TAMs. These Th1 polarizing effects of cytokines of TAMs are dose dependent and reach the maximal values at 24 hrs of incubation. Though, we found a significant release of IFN-γ in TAMs without T-cells, and increased level of IFN-γ with T-cells suggests that Hsp70 stimulates T-cells. Summarizing, these data demonstrates that Hsp70 restore Th1 polarizing cytokines production in the TBH and thus ascribe a possibility to develop a novel immunotherapeutic regime by using TAMs that could contribute well to the correction of tumor induced immune dysfunction.
IL-13 Rα2-mediated interleukin-13 neutralization represses in vivo progressive growth of a T-cell lymphoma
(2007) P. Deepak; K. Sanjay; A. Acharya
Dalton's lymphoma (DL) is a T-cell lymphoma of spontaneous origin, characterized by highly invasive and malignant nature, killing the host in a very short period of life span. DL-bearing host is reflected by very high titer of IL-13 in serum. Therefore, we hypothesized that over expression of IL-13 may greatly affect the growth of DL-cells in a tumor-bearing host. In this study, to assess the involvement of IL-13 in DL-cell progression, we have blocked the IL-13 activity/signalling by the systemic delivery of non-signaling decoy receptor IL-13 Rα2, and IL-13 level vs DL-cell proliferation were measured. We observed that systemic delivery of IL-13 Rα2 inhibits the DL-cell progression in much extent and enhances the survival and longevity of DL-bearing mice. Further, this study re-inforce the therapeutic advantage of IL-13 Rα2 in a T-cell lymphoma tumor system.
Interleukin-13 induces T helper type 2 immune responses in OVA-immunized BALB/c mice bearing a T cell lymphoma
(2012) P. Deepak; A. Acharya
T lymphocytes play a crucial role in the regulation of immune responses against the tumour cells. Tumour progression results in dysfunction and inhibition of T cells, which ultimately leads to impairment in the antitumour immune response. The impaired antitumour immune response in the host is represented by the decreased number of T cells and their incomplete and improper function. The immunosuppressive network in tumour-bearing host mediated by tumour cells also leads to the inequities of T cell subsets and imbalance of Th1/Th2 dichotomy. Therefore, in the present study, we sought to investigate the role of tumour progression in the development of T cell phenotype and the involvement of interleukin-13 thereof selecting Dalton's lymphoma (DL) as a tumour model. It was observed that a significant increase in the number of CD4 + T cell population, whereas a significant decline in the CD8 + T cells among lymphoid cell population of OVA-immunized DL-bearing BALB/c mice occurs. Similar observation was found following the administration of IL-13 to the normal healthy mice. It was further confirmed that expansion in Th2 type cells among CD4 + T cell population occurs following the progression of tumour and administration of IL-13 to normal healthy mice by an yet to define mechanism. Therefore, it can be concluded that IL-13 has immense role in polarizing the immune responses by inducing the differentiation of Th2 type of cells. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.
Interleukin-13-induced type II polarization of inflammatory macrophages is mediated through suppression of nuclear factor-κB and preservation of IκBα in a T cell lymphoma
(2007) P. Deepak; S. Kumar; A. Acharya
Spontaneously arising transplantable T cell lymphoma, designated as Dalton's lymphoma (DL), is characterized by a highly invasive and deleterious nature almost completely paralysing the host immune system. The level of interleukin (IL)-13 is elevated in serum and ascitic fluid of the DL-bearing host. IL-13 is a potent immunosuppressive cytokine and is an alternative activator of macrophages that suppresses the production of nitric oxide (NO) and expression of inducible nitric oxide synthase (iNOS), and proinflammatory cytokines. The expression of iNOS and proinflammatory cytokines are dependent largely upon the activation of nuclear factor-κB (NF-κB). Activation of NF-κB involves the degradation of cytoplasmic inhibitor IκBα, allowing the nuclear translocation of NF-κB and thereby transcription of the iNOS gene. Therefore, in this study we sought to determine whether the alternative activation or type II polarization of macrophages induced by IL-13 is mediated by the suppression of NF-κB and cytoplasmic preservation of IκBα. Western blot analysis and electrophoretic mobility shift assay (EMSA) indicate that tumour-associated macrophages (TAM) or polarized type II macrophages are due to preserved protein expression of IκBα, and therefore suppressed NF-κB nuclear translocation. These findings suggest that IL-13 may operate through the suppression of NF-κB activation and preservation of IκBα. © 2007 British Society for Immunology.
Mn(II) catalyzed synthesis of 5(4-hydroxyphenyl)-2-(N-phenylamino)-1,3,4-oxadiazole: Crystal structure, DFT, molecular docking, Hirshfeld surface analysis, and in vitro anticancer activity on DL cells
(Elsevier B.V., 2022) M.K. Gond; Alok Shukla; Shivendra Kumar Pandey; M.K. Bharty; B. Maiti; A. Acharya; N. Tiwari; D. Katiyar; R.J. Butcher
The syntheses and screening of novel synthetic molecules have gained attention as a potential therapeutic agent in the treatment of cancer. In the present study, a new compound 5(4-hydroxyphenyl)-2-(N-phenylamino)-1,3,4-oxadiazole (Hppo) has been synthesized and its anticancer activity is investigated against Dalton's lymphoma (DL) tumor cells derived from murine T-cell lymphoma. The Hppo has been characterized through IR, NMR, and single-crystal X-ray data. The structure of Hppo is stabilized via hydrogen bonding interactions and crystallizes in an orthorhombic system with space group P b c n. The fingerprint plots associated with Hirshfeld surface analysis indicate that there are different types of weak interactions viz. C-H···N, O-H···N and C-H···O. The DFT calculations are also performed to verify physiochemical properties of Hppo and the results obtained are in good agreement with the experimental results. The HOMO and LUMO energy gap of 7.344 eV for Hppo indicates good NLO properties. The cytotoxicity activity of Hppo is tested against Dalton's lymphoma cells using MTT assay which reveals that the compound showed admirable anticancer activity (IC50= 50 µg/mL), which is better than many previously reported compounds. The mechanism of action of Hppo is investigated by performing different biological studies and the results obtained reveal that Hppo acts through down-regulating mitochondrial membrane potential and up-regulating reactive oxygen species production. Molecular docking studies are also performed to obtain more insights on biological activities of Hppo and its mode of action against CYP-19 (PDB: 3EQM), JAK2 (PDB: 5AEP), BCL-2 (PDB: 2O2F), and caspase3 (PDB: 1RE1), and result displayed favorable binding interactions with binding energy -7.43, -7.96, -6.61, and -6.88 Kcal/mol. © 2021 Elsevier B.V.
Morphological effects of autologous hsp70 on peritoneal macrophages in a murine T cell lymphoma
(IOS Press BV, 2013) P.K. Gautam; S. Kumar; P. Deepak; A. Acharya
Heat shock protein 70 is highly conserved cytosolic protein which have important role in growth, development, and apoptosis. Hsp70 is well-known activator of macrophages and enhances the release of specific and non-specific effector molecules that have major role in tumor destruction and immunopotentiation of host. However, morphological effects of hsp 70 has not been carried out, therefore, morphological effects of hsp 70 on murine peritoneal macrophages were examined by light microscopy and scanning electron microscopy. Thioglycolate-induced peritoneal macrophages were prepared from BALB/c mice and cultured for 24 h in the presence of the hsp70. Tumor-associated macrophages treated with 10 μg/ml were varied in shape, mostly spindle shaped, i.e., stretched bidirectionally; surface ruffles were increased and their lamellipodia was prominent which suggest that hsp 70 treatment not only enhances the functional state of the peritoneal macrophages but also initiate immense morphological changes leading to increased endothelium adherence, increased antigen uptake, and increased migration to the inflammatory site. © 2013 International Society of Oncology and BioMarkers (ISOBM).
Novel peptide treated macrophage induces apoptosis in tumor cell line P815
(Biolife, 2004) A. Acharya; V. Tripathi
In vitro macrophages treated with novel peptides have been shown to develop enhanced tumoricidal activity against tumor target cell (P815), though the exact mechanism is not known. In the present study, we have investigated the mechanism involved in the tumor cell cytotoxicity mediated by novel peptides treated macrophage and involvement of possible effectors molecule. Peritoneal exudated macrophages treated with LPS, peptides, and LPS plus peptides and when cocultured with tumor cell P815 caused tumor cell death by induction of apoptosis. The results of our experiment reveal a specific pattern of intranucleosomal DNA fragmentation detected by agarose gel electrophoresis and also with microscopic examination of the cells revealed nuclear alteration characteristic of apoptosis. Viability studies showed that most of the cells undergoing apoptosis were found to be non-viable even after 24 h coculture. Macrophage induced apoptosis in tumor target cells even in the absence of cell to cell contact through diffusible effectors molecule. The study thus shows that the novel peptide treated macrophage can kill tumor cell P815 by extracellular release of effectors molecule NO (nitric oxide) that act by inducing apoptosis in a target cell-specific manner. Copyright © by BIOLIFE, s.a.s.
Novel peptides enhance the production of nitric oxide and inducible nitric oxide synthase (iNOS) gene expression in murine macrophage
(Biomedical Research Press s.a.s., 2003) A. Acharya; V. Tripathi
Bioactive novel polypeptide of Anurans skin has a wide range of antimicrobial properties against the infection and tumour cell. Macrophages are known to produce the Nitric oxide (NO) by a variety of cells upon activation. NO produced by the activated macrophages an important mediator for antimicrobial and tumoricidal activity. In-vitro macrophage exposed with medium alone, containing LPS, containing polypepeptides and LPS + polypeptides for 24 h showed enhanced production of NO with respect to control and LPS treated and significant increase in NO production in LPS + polypeptide. Western blot and PCR analysis also showed that increased production of protein expression and mRNA expression of inducible nitric oxide synthase (iNOS). These findings suggest that novel polypeptides are potent activating agent for enhanced production of NO through activation of iNOS gene.
Role of macrophage in tumor microenvironment: Prospect in cancer immunotherapy
(Biolife s.a.s., 2013) P.K. Gautam; P. Deepak; S. Kumar; A. Acharya
Current evidence suggests an increasing role of macrophages in inflammation and tumor progression. Most tumors contain an abundant number of macrophages as a major component of their leukocyte infiltrate, which co-exist with tumor cells at the tumor microenvironment. Upon activation with soluble tumor antigens, macrophages release a distinct repertoire of growth factor, cytokines, chemokines and enzymes that inhibit growth of the tumor. However, the anti-tumor immune response induced by macrophages does not always ensue. Tumor cells themselves are capable of down-regulating macrophage phenotype and functions and anti-tumor immune responses in the tumor-bearing host. The present review aims to elucidate the role of macrophages in tumor growth and progression, invasion, metastasis, and angiogenesis at the site of tumor growth. Moreover, the effect of tumor microenvironment on the phenotype and function of macrophages, which are altered due to the continuous exposure of various soluble and non-soluble tumor promoting factors secreted by tumor cells, and implication of macrophages in cancer immunotherapy have been discussed in detail. Copyright © by BIOLIFE, s.a.s.
Selenium nanoparticles induce suppressed function of tumor associated macrophages and inhibit Dalton's lymphoma proliferation
(Elsevier B.V., 2017) Pramod Kumar Gautam; Sanjay Kumar; M.S. Tomar; Rishi Kant Singh; A. Acharya; Sanjay Kumar; B. Ram
Selenium Nanoparticle (SeNPs) is reported that it enhances and maintains optimal immune during infection and malignancies. To this end, we examined the role of selenium on TAMS whose anti-tumor function suppressed which favor tumor progression. BALB/c (H2d) strain of mice non-Hodgkin type of Dalton's cell line was used to check the role of carboxlic group induced, synthesized SeNPs on TAMs. Screening of IC50 value was done primarily trypen blue exclusion assay and 50% proliferation of DL cells inhibited 40 ng/ml to 50 ng/. Treatment also decreases ΔΨm, fragmentation of DNA of DL cells and arrest cells cycle in G1/G0 phage. Untreated TAMs cells showing suppressed expression of ROS, adhesion, phagocytosis, fusion and receptor profiling such as ICAM-1, CD47, CD172α. Which was induced more as compare to untreated group. SeNPs have potential to induce the anti-tumor function of TAMs whose anti-tumor function down-regulated pliable shifted towards tumor progression. It decreased the proliferation of DL cell by inducing apoptosis. Therefore, the synthesized SeNPs could be used for imaging diagnosis and cancer therapy which must be cost effective with negligible side effects shifted towards tumor progression. It decreased the proliferation of DL cell by inducing apoptosis. © 2017
Solvent-dependent crystallization and anti-cancer activities based on Ni(II) and Co(II) complexes of 1-picolinoyl-4-phenyl-3-thiosemicarbazide: Synthesis, crystal structure, and photoluminescence study
(Elsevier B.V., 2023) Suryansh Chandra; Shubham Jaiswal; Alok Shukla; Ankit Kumar Singh; Somenath Garai; A. Bharti; A. Acharya; M.K. Bharty
In search of alternative of platinum-based drugs for the treatment of cancer, lead to the development of other potential metallodrug of transition metal complexes. The efficacious and novel experimental content of this paper reports the synthesis of [Ni(Hppts)2].CHCl3 (1a), [Ni(Hppts)2].(CH3)2SO (1b) and [Co(Hppts)2] (2) complexes of 1-picolinoyl-4-phenyl-3-thiosemicarbazide (H2ppts). The synthesized complexes have been characterized by UV-vis., Infrared, and NMR spectrometry. Furthermore, complexes 1a and 1b were characterized by single-crystal X-ray diffraction data. Emission spectra show that, complex 1a exhibits higher fluorescence intensity as compared to that of ligand H2ppts and complex 2. The order of fluorescence intensity was found as complex 1a > complex 2 > H2ppts. Moreover, Complexes 1a and 1b are stabilized via various types of intermolecular interactions. The cytotoxicity of complexes 1a, 2, and ligand was evaluated against Dalton's Lymphoma cells using standard MTT Assay. The anticancer activity results showed that complex 1a significantly reduced cell viability in a dose-dependent manner, whereas H2ppts and complex 2 did not show significant reduction in cell viability of DL cells when compared with the control. The complex 1a IC50 value was determined to be around 40 µg/mL. The anti-tumor activity concludes that the complex 1a has high anti-neoplastic activity on DL cells at low doses. © 2023 Elsevier B.V.
Suppressed expression of homotypic multinucleation, extracellular domains of CD172α (SIRP-α) and CD47 (IAP) receptors in TAMs upregulated by Hsp70-peptide complex in Dalton's lymphoma
(Blackwell Publishing Ltd, 2014) P.K. Gautam; A. Acharya
CD172α and CD47 are members of glycoprotein expressed on macrophages and various immune cells, promote immune recognition and T cell stimulation that priming phagocytosis of pathogens and apoptotic bodies and malignant cell. Tumour-releasing immunosuppressive factor promotes tumour growth and transforms the tumour resident M1 phenotype of macrophage to M2 phenotype (TAMs) that promotes tumour progression by downregulating the expression of different surface receptor including CD172α and CD47. Recent studies have reported that CD172α and CD47 are involved in the pathogenesis and promote malignancies such as lymphoma, leukaemia, melanoma, lung cancer and multiple myeloma, and their expression varies during infection and malignancies. Autologous Hsp70 is well recognized for its role in activating macrophages leading to enhance production of inflammatory cytokines. It has been observed that Hsp70 derived from normal tissues do not elicit tumour immunity, while Hsp70 preparation from tumour cell was able to elicit tumour immunity. However, the role of exogenous autologous hsp70 on the formation of giant cells is completely unknown. Therefore, in the present study, we sought to investigate the effect of Hsp70-peptide complex on the expression of CD172α and CD47 receptors in normal peritoneal macrophages (NMO) and TAMs. Finding shows that the expression of CD172α and CD47 enhances in TAMs and it reverts back the suppressed function of TAMs into M1 state of immunoregulatory phenotype that promotes tumour regression by enhanced multinucleation and phagocytosis of malignant cells and significantly enhances the homotypic fusion of macrophages and polykaryon formation in vitro by enhancing the expression of SIRPα and IAP. © 2014 John Wiley & Sons Ltd.
Synthesis, characterizations, crystal structure and anticancer activity of Mn(II), Co(II) and Ni(II) complexes of N′-cyclohexyl-2-thiophene-carbonyl hydrazine carbothioamide
(Elsevier Ltd, 2023) Shubham Jaiswal; Lokesh Yadav; Shivendra Kumar Pandey; Suryansh Chandra; M.K. Bharty; L.B. Prasad; A. Acharya
The current century has witnessed continuous and exponential increase in the number of patients suffering from different types of sarcomas. To cure these sarcomas, there are continuous efforts to develop more efficient and less cytotoxic anti-cancerous and antitumor drugs. A thiosemicarbazide derived N-cyclohexyl-2-thiophene-carbonyl hydrazine carbothioamide (Htach) and its metal complexes [Mn(tach)2(o-phen)] (1), [Co(tach)2(o-phen)] (2), [Ni(tach)2(o-phen)] (3) were synthesized and reported here. In these complexes, o-phen was used as secondary ligand for coordinatively saturation of metal ions. The synthesized ligand and complexes are well characterized with different elemental analysis FT-IR, and UV–visible and HR-MS spectroscopy. Further, Complex 1 was characterized by single XRD and crystallized in monoclinic system with space group P 21/n. The anti-proliferative potential of ligand and its complexes were evaluated against Dalton's lymphoma (DL) cancer cell lines through MTT, AO/EtBr and DAPI based assays. The effect of these metal complexes on normal cell lines (splenocyte) has been also investigated. Our investigation reveals that metal–ligand complexes have significant strong anticancer activity against tumor cells in a dose-dependent mode, whereas minimal effect on normal cell lines. For ligand and complexes 1–3, the IC50 values were found as 20, 10, 20 and 5 µM, respectively. These results suggest that among Mn, Co and Ni complexes, nickel complex will be more effective for the functionalization of anticancer agents. © 2023 Elsevier Ltd