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PublicationArticle 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 AcharyaPurpose: 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.PublicationArticle A benzophenanthridine alkaloid, chelerythrine induces apoptosis in vitro in a Dalton′s lymphoma(2013) Sanjay Kumar; Praveen Deepak; Pramod Gautam; Arbind AcharyaPurpose: 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.PublicationArticle Testicular changes in rat exposed to Trichloroacetic acid (TCA) during organogenesis(2005) Royana SinghHalogenated hydrocarbons such as Trichloroacetic acid (TCA) are among the most common water supply contaminants in the world. The study was, therefore undertaken to examine the effect of Trichloroacetic acid on the developing testis of Charles foster rat. The rats were randomly placed in the test groups and exposed to various concentrations of TCA i.e. 1000, 1200, 1400, 1600 and 1800 mg/Kg body weight by oral gavage throughout the period of organogenesis, from day 6 to 15 of gestation. TCA was administered in the form of sodium trichloroacetate, which in the body is reduced to trichloroacetic acid by P450 enzyme in the liver. TCA administration led to dose related reduction in the fetal weight and the testicular weight, when they were collected on day 19 of gestation. Control mothers were administered equal volume of distilled water. Histological studies of the testis when compared to the controls revealed decrease in the length and diameter, of the seminiferous tubules with 1400 mg/kg and higher doses. The rapid assault on the cellular components with the increase in the TCA concentration causing enhanced apoptosis of the gonocytes were well evident, with the sub-sequel lying in the total reduction in the testicular size.PublicationArticle Gender-specific antitumor action of aspirin in a murine model of a T-cell lymphoma bearing host(2012) Anjani Kumar; Naveen Kumar Vishvakarma; Alok Chandra Bharti; Sukh Mahendra SinghAspirin is an anti-inflammatory drug demonstrated to possess a tremendous anticancer potential. As progression of some tumors is influenced by sex hormones, we investigated if the antineoplastic action of aspirin shows gender dependence. Using a murine model of T-cell lymphoma, the present investigation was undertaken to study if the antitumor actions of aspirin against lymphoma cells display gender dimorphism. The findings of the present investigation indicate that aspirin administration to male and female tumor-bearing hosts resulted in gender dependent differential tumor growth retardation. Such gender dichotomy of aspirin's antitumor action was associated with a differential impact on cell cycle progression and expression of cell survival regulatory molecules. Aspirin administration was also found to modulate crucial parameters of tumor microenvironment, including contents of glucose, lactate and cell growth regulatory cytokines, in a gender specific manner. Aspirin was found to reverse estrogen-dependent augmentation of tumor cell survival in vitro. Taken together the results of the present study suggest that the antineoplastic action of aspirin is gender-dependent and should be considered in designing of gender-specific therapeutic applications of aspirin. © 2011 Elsevier Inc..PublicationArticle Epinephrine facilitates the growth of T cell lymphoma by altering cell proliferation, apoptosis, and glucose metabolism(Elsevier Ireland Ltd, 2023) Rajan Kumar Tiwari; Shiv Govind Rawat; Vishal Kumar Gupta; Pradip Kumar Jaiswara; Pratishtha Sonker; Santosh Kumar; Vibhav Gautam; Manoj K. Mishra; Ajay KumarIn recent years, studies have reported the role of stress-regulatory hormones, including epinephrine, in regulating the progression of a few cancers. However, the tumor-promoting action of epinephrine is not yet investigated in T cell malignancy, a rare and complicated neoplastic disorder. More so, very little is known regarding the implication of epinephrine in the glucose metabolic rewiring in tumor cells. The present investigation showed that epinephrine enhanced the proliferation of T lymphoma cells through up- and down-regulating the expression of PCNA, cyclin D, and p53, respectively. In addition, epinephrine inhibited apoptosis in T lymphoma cells possibly by increasing the level of BCL2 (an anti-apoptotic protein) and decreasing PARP level (a pro-apoptotic protein). Intriguingly, epinephrine is reported to stimulate glycolysis in T lymphoma cells by increasing the expression of crucial glycolysis regulatory molecules, namely HKII and PKM2, in a HIF-1α-dependent manner. Moreover, augmented production of ROS has been observed in T lymphoma cells, which might be a central player in epinephrine-mediated T cell lymphoma growth. Taken together, our study demonstrates that epinephrine might have a significant role in the progression of T cell lymphoma. © 2022PublicationArticle Loss of non-muscle myosin II Zipper leads to apoptosis-induced compensatory proliferation in Drosophila(Elsevier B.V., 2025) Dipti Verma; Bappi Sarkar; Jyoti K. Singh; Ankita Singh; M. Mutsuddi; Ashim MukherjeeDrosophila Non-muscle myosin II Zipper (Zip) belongs to a functionally divergent class of molecular motors that play a vital role in various cellular processes including cell adhesion, cell migration, cell protrusion, and maintenance of polarity via its cross-linking property with actin. To further determine its role in cell proliferation and apoptosis, we carried out Zip loss of function studies that led to compromised epithelial integrity in Drosophila wing imaginal discs as evident from the perturbed expression pattern of cell-cell junction proteins Cadherin, Actin, and Armadillo. Disruption of these adhesion proteins resulted in the cells undergoing apoptosis as evident from the increased level of effector caspase, cDcp-1. The induction of cell death due to the loss of function of Zip was accompanied by proliferation as apparent from increased PH3 staining. The control of apoptosis-induced compensatory proliferation lies under the caspase cascade. We carried out experiments that suggested that the apical caspase Dronc is responsible for the apoptosis-induced compensatory proliferation due to the loss of Zip function and not the effector caspase Drice/Dcp-1. Further, it was observed that Dronc leads to the subsequent activation of Jun N-terminal kinase pathway (JNK) pathway and Wingless (Wg) mitogen that diffuse to the neighboring cells and prompt them to undergo cell division. Taken together, our results suggest that loss of function of Zip leads to apoptosis-induced compensatory proliferation. © 2025PublicationArticle Melatonin induces apoptosis and cell cycle arrest in cervical cancer cells via inhibition of NF-κB pathway(Springer Science and Business Media Deutschland GmbH, 2022) Tarun Minocha; Megha Das; Vipin Rai; Sumit Singh Verma; Nikee Awasthee; Subash Chandra Gupta; Chandana Haldar; Sanjeev Kumar YadavCervical cancer is the most prevalent cancer in females. Melatonin, a neurohormone has been documented as a promising therapeutic molecule for cervical cancer. However, the underlying molecular mechanism is not known. We explored the dose-dependent anti-tumor response of melatonin against cervical cancer cell lines, HeLa (HPV-18 positive) and SiHa (HPV-16 positive). The anti-cancer effect of melatonin was evaluated by MTT assay, cell imaging, colony formation, DAPI, AO/PI, LDH, Flow cytometry, scratch assay, western blot analysis and real-time PCR. Results of DAPI, AO/PI, LDH, and Annexin/PI staining revealed that melatonin induces apoptosis. The results of cell cycle analysis revealed that melatonin arrests the HeLa and SiHa cells in sub-G1 and G1 phases, respectively. Western blot analysis revealed that melatonin downregulated the expression of pro-inflammatory transcription factor, NF-κB and the expression of COX-2 protein, a key mediator in cell proliferation. In addition, melatonin downregulated the expression of an invasive marker, MMP-9, an antiapoptotic protein, Bcl-2, and upregulated the expression of pro-apoptotic protein, Bax at both transcriptional and translational levels. Overall, the results suggest that melatonin exhibited strong anti-cancer therapeutic potential against human cervical cancer cell line progression possibly through inhibition of NF-κB signalling pathway. © 2022, The Author(s), under exclusive licence to Springer Nature Switzerland AG.PublicationArticle Leishmania donovani infection activates Toll-like receptor 2, 4 expressions and Transforming growth factor-beta mediated apoptosis in renal tissues(Elsevier Editora Ltda, 2017) Vinod Kumar; Neeraj Tiwari; Mallikarjuna Rao Gedda; Rizwanul Haque; Rakesh K. SinghThe present study was aimed to identify the underlying mechanisms of improper renal function in Leishmania donovani infection that causes VL. Mice (BALB/c) were infected with L. donovani and different parameters for proteinuria were assessed. The levels of superoxide anion (O2−), hydrogen peroxide (H2O2), lipid peroxidation (MDA), inflammatory cytokines, and toll-like receptor (TLR) 2 and 4 expression were found significantly elevated at 60th day in these animals and declined at 90th day post infection. However, TGF-β and caspase 3 activities were higher at 90th day in comparison to 60th day post infection. These findings suggested that exacerbated inflammatory conditions correlate with abnormal renal functions in L. donovani infection, which is further augmented by activated TLRs expressions by circulating leishmanial antigens. Further, the increased levels of TGF-β and caspase 3 at 90th day suggested TGF-β mediated apoptotic cell death of renal and other cells during later stages of disease that may eventually result in release of host and parasitic factors in urine during visceral leishmaniasis. © 2017 Sociedade Brasileira de InfectologiaPublicationArticle Role of host's antitumor immunity in exercise-dependent regression of murine T-cell lymphoma(2005) Mahendra Pal Singh; Gajendra Singh; Sukh Mahendra SinghWe have reported that the ascitic growth of a transplantable T cell lymphoma of spontaneous origin, designated as Dalton's lymphoma (DL), is associated with a concomitant immunosuppression. We have also reported that progressive in vivo growth of DL resulted in an inhibition of macrophage functions. In present investigation we report that physical exercise by DL-bearing mice, on a treadmill on a daily basis for various time durations for 10 days, increased the life span along with an inhibition of tumor growth. A significant decrease in the volume of ascitic fluid and number of cells in the tumor was obtained in mice, which underwent exercise. DL cells obtained from exercised groups showed a decreased proliferation in vitro. An augmentation in the percent of cells showing apoptotic morphology and percent specific DNA fragmentation was observed, suggesting that physical exercise increased the incidence of apoptosis in tumor cells. Moreover, macrophages obtained from tumor-bearing mice, which underwent exercise training, showed an augmented tumoricidal activity and production of tumoricidal molecules like interleukin-1 (IL-1), tumor necrosis factor (TNF) and nitric oxide (NO). On the basis of this study it is suggested that the regression of tumor growth consequent to physical exercise training of tumor bearing host, may be due to an exercise-dependent augmentation of macrophage tumoricidal functions. © 2005 Elsevier Ltd. All rights reserved.PublicationArticle Withania somnifera Alleviates Parkinsonian Phenotypes by Inhibiting Apoptotic Pathways in Dopaminergic Neurons(Springer Science and Business Media, LLC, 2014) Jay Prakash; Shikha Chouhan; Satyndra Kumar Yadav; Susan Westfall; Sachchida Nand Rai; Surya Pratap SinghManeb (MB) and paraquat (PQ) are environmental toxins that have been experimentally used to induce selective damage of dopaminergic neurons leading to the development of Parkinson’s disease (PD). Although the mechanism of this selective neuronal toxicity in not fully understood, oxidative stress has been linked to the pathogenesis of PD. The present study investigates the mechanisms of neuroprotection elicited by Withania somnifera (Ws), a herb traditionally recognized by the Indian system of medicine, Ayurveda. An ethanolic root extract of Ws was co-treated with the MB–PQ induced mouse model of PD and was shown to significantly rescue canonical indicators of PD including compromised locomotor activity, reduced dopamine in the substantia nigra and various aspects of oxidative damage. In particular, Ws reduced the expression of iNOS, a measure of oxidative stress. Ws also significantly improved the MB + PQ mediated induction of a pro-apoptotic state by reducing Bax and inducing Bcl-2 protein expression, respectively. Finally, Ws reduced expression of the pro-inflammatory marker of astrocyte activation, GFAP. Altogether, the present study suggests that Ws treatment provides nigrostriatal dopaminergic neuroprotection against MB–PQ induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects. © 2014, Springer Science+Business Media New York.