BHU Institutional Repository :: Browsing by Author "Shukla, Alok"

Browsing by Author "Shukla, Alok"

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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) Verma, Praveen Kumar; Singh, Rishi Kant; Kumar, Sandeep; Shukla, Alok; Kumar, Sanjay; Gond, Mannu Kumar; Bharty, Manoj Kumar; Acharya, Arbind
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.
Evidence that PKC? inhibition in Dalton's Lymphoma cells augments cell cycle arrest and mitochondrial-dependent apoptosis
(Elsevier Ltd, 2022) Singh, Rishi Kant; Verma, Praveen Kumar; Kumar, Sandeep; Shukla, Alok; Kumar, Naveen; Kumar, Sanjay; Acharya, Arbind
Protein kinase C? (PKC?), belonging to ser/thr protein kinase, perform various biological functions. Overexpression of PKC? has been observed in multiple human malignancies including lymphoma. However, the molecular pathogenesis and involvement of PKC? in Non-Hodgkin lymphoma (NHL) are not clearly understood. Hence, deciphering the role of PKC? in NHL management may provide a better therapeutic option. In the present study, we used selective pharmacological inhibitors G�6976 and Ro320432 that potentially inhibit PKC?-mediated signaling in DL cells, resulting in the inhibition of cell growth and mitochondrial-dependent apoptosis. PKC? 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 PKC? in NHL, and provided potential implications for its therapy. � 2022 Elsevier Ltd
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) Gond, M.K.; Shukla, Alok; Pandey, Shivendra Kumar; Bharty, M.K.; Maiti, B.; Acharya, A.; Tiwari, N.; Katiyar, D.; Butcher, R.J.
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 �g/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.
Moringa oleifera L. leaf extract induces cell cycle arrest and mitochondrial apoptosis in Dalton's Lymphoma: An in vitro and in vivo study
(Elsevier Ireland Ltd, 2023) Kumar, Sandeep; Verma, Praveen Kumar; Shukla, Alok; Singh, Rishi Kant; Patel, Anand Kumar; Yadav, Lokesh; Kumar, Sanjay; Kumar, Naveen; Kaushalendra; Acharya, Arbind
Ethnopharmacological relevance: The present work is based on a wide spectrum of evidences available from scientific literature which reflects nutritional and medicinal values of natural products such as plants and their extracts. Moringa oleifera is one such popular plant species amidst indigenous tribal communities which is frequently used to treat ailments such as piles, sore throat, eye and ear infections and even poisonous bites of tropical fauna such as insects or snakes. Furthermore decoction of leaf and bark was used to cure fever and cough. Evidences further reveal that Moringa oleifera L. (Family Moringaceae), is widely distributed not only over the Indian sub-continent, but also over Philippines, Central America, Saudi Arabia and the Caribbean Islands and have been traditionally used to treat cancers since ancient times. However, therapeutic effects of Moringa oleifera on Non-Hodgkin Lymphoma (NHL) are yet to be established. Aim of the study: The study aims to investigate the anti-cancer effects of Moringa oleifera leaf extract against murine NHL Non-Hodgkin cells in vitro and in vivo. Material and methods: The pharmacologically active compounds of Moringa oleifera leaf extract were identified by GC-HRMS analysis. Tests of Moringa oleifera leaf extract's cytotoxicity against DL cells were carried out using the MTT assay. Chromatin condensation along with other morphological alterations were visualized through Fluorescence microscopy. Changes in the mitochondrial membrane potential (??m), the cell cycle, and apoptosis were analysed through flow cytometer. We tried to identify proteins involved in apoptosis and cell cycle through Western blotting using BALB/c mice as a model organism. Results: GC-HRMS study revealed that a methanol based leaf extract of Moringa oleifera (MOML) comprises of a variety of bioactive chemicals. Our results indicate that MOML successfully reduced the proliferation of DL cells by lowering ??m, changing overall cell morphology. DL cells treated with MOML showed arrested cell cycle at the G2/M phase and substantially up-regulated the expression of p53 and p21. Elevated levels of Bax, Cyt-c, and Caspase-3 and lowered expression levels of Bcl-2 protein suggested induction of apoptosis. Mechanistically, the anticancer efficacy of MOML is attributed to MEK/ERK-mediated pathway inactivation in DL cells. It is also interesting to note that MOML-mediated inhibition of DL growth was accompanied by apoptosis induction and improvement in hematological parameters in DL-bearing mice. Conclusion: Our finding suggested that MOML induces apoptosis and abrogates the growth of Dalton's lymphoma both in vitro and in vivo. � 2022 Elsevier B.V.
Potential implications of protein kinase C? in pathophysiological conditions and therapeutic interventions
(Elsevier Inc., 2023) Singh, Rishi Kant; Kumar, Sanjay; Kumar, Sandeep; Shukla, Alok; Kumar, Naveen; Patel, Anand Kumar; Yadav, Lokesh Kumar; Kaushalendra; Antiwal, Meera; Acharya, Arbind
PKC? is a molecule with many functions that play an important role in cell survival and death to maintain cellular homeostasis. Alteration in the normal functioning of PKC? is responsible for the complicated etiology of many pathologies, including cancer, cardiovascular diseases, kidney complications, neurodegenerative diseases, diabetics, and many others. Several studies have been carried out over the years on this kinase's function, and regulation in normal physiology and pathological conditions. A lot of data with antithetical results have therefore accumulated over time to create a complex framework of physiological implications connected to the PKC? function that needs comprehensive elucidation. In light of this information, we critically analyze the multiple roles played by PKC? in basic cellular processes and their molecular mechanism during various pathological conditions. This review further discusses the current approaches to manipulating PKC? signaling amplitude in the patient's favour and proposed PKC? as a therapeutic target to reverse pathological states. � 2023 Elsevier Inc.
Safety Assessment of a Nucleoside Analogue FNC (2�-deoxy-2�-?-fluoro-4�-azidocytidine ) in Balb/c Mice: Acute Toxicity Study
(Asian Pacific Organization for Cancer Prevention, 2023) Kumar, Naveen; Delu, Vikram; Shukla, Alok; Singh, Rishi Kant; Ulasov, Ilya; Fayzullina, Daria; Kumar, Sandeep; Patel, Anand Kumar; Yadav, Lokesh; Tiwari, Ruchi; Rachana, Kumari; Mohanta, Shivashish Priyadarshi; Kumar, Sanjay; Kaushalendra, Kaushalendra; Acharya, Arbind
Objectives: The present study aimed to provide an insight into the acute toxicity of a novel fluorinated nucleoside analogue (FNA), FNC (Azvudine or2�-deoxy-2�-?-fluoro-4�-azidocytidine). FNC showed potent anti-viral and anticancer activities and approved drug for high-load HIV patients, despite, its acute toxicity study being lacking. Materials and Methods: OECD-423 guidelines were followed during this study and the parameters were divided into four categories - behavioral parameters, physiological parameters, histopathological parameters, and supplementary tests. The behavioral parameters included feeding, body weight, belly size, organ weight and size, and mice behavior. The physiological parameters consisted of blood, liver, and kidney indicators. In histopathological parameters hematoxylin and eosin staining was performed to analyse the histological changes in the mice organs after FNC exposure. In addition, supplementary tests were conducted to assess cellular viability, DNA fragmentation and cytokine levels (IL-6 and TNF-?) in response to FNC. Results: In the behavioral parameters FNC induced changes in the mice-to-mice interaction and activities. Mice�s body weight, belly size, organ weight, and size remained unchanged. Physiological parameters of blood showed that FNC increased the level of WBC, RBC, Hb, and neutrophils and decreased the % count of lymphocytes. Liver enzymes SGOT (AST), and ALP was increased. In the renal function test (RFT) cholesterol level was significantly decreased. Histopathological analysis of the liver, kidney, brain, heart, lungs, and spleen showed no sign of tissue damage at the highest FNC dose of 25 mg/kg b.wt. Supplementary tests for cell viability showed no change in viability footprint, through our recently developed dilution cum-trypan (DCT) assay, and Annexin/PI. No DNA damage or apoptosis was observed in DAPI or AO/EtBr studies. Pro-inflammatory cytokines IL-6 and TNF-? increased in a dose-dependent manner. Conclusion: This study concluded that FNC is safe to use though higher concentration shows slight toxicity. � This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.
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) Chandra, Suryansh; Jaiswal, Shubham; Shukla, Alok; Singh, Ankit Kumar; Garai, Somenath; Bharti, A.; Acharya, A.; Bharty, M.K.
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 �g/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.

Browsing by Author "Shukla, Alok"

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