Browsing by Author "Verma, Praveen Kumar"
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Publication Achyranthes aspera L. leaf extract induced anticancer effects on Dalton's Lymphoma via regulation of PKC? signaling pathway and mitochondrial apoptosis(Elsevier Ireland Ltd, 2021) Singh, Rishi Kant; Verma, Praveen Kumar; Kumar, Amit; Kumar, Sandeep; Acharya, ArbindEthnopharmacological 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 (??m) 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 C? (PKC?) 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 PKC? pathway and induction of apoptosis. Our result suggested that AAML promotes mitochondrial apoptotic cascade in DL cells by suppressing the PKC? signaling pathway. Conclusion: The study suggests that AAML could potently suppress DL progression by promoting apoptosis via mitochondrial-cascade and attenuation of the PKC? signaling pathway. � 2021Publication 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, ArbindPurpose: 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.Publication Electrocatalytic oxygen evolution and antiproliferative activity of Co(III) complexes stabilized by in situ generated bis(5-furan/phenyl-1,2,4-triazole)-3-sulfinamide(John Wiley and Sons Ltd, 2022) Bharty, Manoj Kumar; Singh, Aarti; Bharati, Pooja; Pandey, Shivendra Kumar; Singh, Devesh Kumar; Ganesan, Vellaichamy; Verma, Praveen Kumar; Acharya, Arvind; Bharti, Akhilesh; Butcher, Ray J.Electrocatalytic water oxidation by transition metal complexes is an emerging area of research. Here, two cobalt(III) complexes [Co(ftsm)NH3(o-phen)]�H2O (1) {ftsm�= bis(5-furan-1,2,4-triazole)-3-sulfinamide} and [Co(ptsm)NH3(o-phen)]�CH3OH (2) {ptsm = bis(5-phenyl-1,2,4-triazole)-3-sulfinamide} were synthesized and characterized by various spectroscopic and X-ray crystallography techniques. Complexes 1 and 2 were found to have admirable electrocatalytic activity towards oxygen evolution reaction (OER). The Tafel slope values for GC/Nf-Complex-2 and GC/RuO2 were 53 and 60 mV/dec, respectively. Consequently, complex 2 possesses a better water oxidation response than standard material RuO2. The ligands Haftt, Haptt, o-phen, and complexes 1 and 2 were also tested for their cytotoxicity against Dalton's lymphoma (DL) cells employing MTT assay and found to have significant cytotoxicity. The IC50 values of Haftt, Haptt, mixed ligands Haftt�+ o-phen and Haptt�+ o-phen, and complexes 1 and 2 against DL cells were found to be 150, 400, 200, 450, 80, and 5�?M, respectively. The complexes were found to have minimal effect on normal cells. The remarkable IC50 value for complex 2 shows that it can be utilized as a potential anticancer agent against DL cells. � 2021 John Wiley & Sons, Ltd.Publication 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, ArbindProtein 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 LtdPublication Mitochondrial pathway mediated apoptosis and cell cycle arrest triggered by cobalt(III) complex in Dalton�s lymphoma cells(Open Science Publishers LLP Inc., 2021) Verma, Praveen Kumar; Gond, Mannu Kumar; Bharty, Manoj Kumar; Acharya, ArbindCancer is a group of diseases which evolves from uncontrolled growth of abnormal cells. It has become the second leading cause of death worldwide. Many platinum-based compounds like cisplatin and carboplatin are widely used as a therapeutic approach against cancer, but patients are resistant to these therapeutic agents with life-threatening side effects. In this study, we used a non-platinum-based compound, i.e. cobalt complex, on the Dalton�s lymphoma cells (DL cells). It is a tumor model of murine T-cell lymphoma of thymic genesis, which is very aggressive. The present study was focused on evaluating the anticancer efficacy of cobalt complex on DL cells. The IC50 value of cobalt complex was found to be 80 �3.21 �M in DL cells�. In addition, cobalt complex promoted condensed nuclei, G1 phase arrest, and induced early and late apoptotic cells. Additionally, flow cytometry examination showed a significant loss in mitochondrial membrane potential and induction of reactive oxygen species after treatment. Furthermore, Western blot revealed the increased p53, cyt-c, Bax protein, and decreased Bcl2 protein level in treated DL cells. These results verified the anticancer properties of cobalt(III) complex against DL cells and propose an alternative therapeutic drug in cancer treatment. � 2021. Praveen Kumar Verma et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).Publication 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, ArbindEthnopharmacological 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.Publication Phytochemical Profiling of Microalgae Euglena tuba and Its Anticancer Activity in Dalton�s Lymphoma Cells(Bioscience Research Institute, 2022) Gupta, Swati Prabha; Siddiqi, Nikhat Jamal; Khan, Haseeb A.; Alrokayan, Salman H.; Alhomida, Abdullah S.; Singh, Rishi Kant; Verma, Praveen Kumar; Kumar, Sandeep; Acharya, Arbind; Sharma, BechanIntroduction: Natural phytochemicals are considered safe to use as therapeutic agents. There is a growing trend toward exploring anticancer effects of crude algal extracts or their active ingredients. Euglena tuba, a microalga, contains excellent antioxidant potential. However, the anticancer property of E. tuba has not been explored. This study investigates the chemical profiling as well as antitumor property of methanolic extract of E. tuba (ETME) against Dalton�s lymphoma (DL) cells. Materials and Methods: E. tuba, procured from northern part of India, was extracted in 70% methanol, dried at room temperature, and stored at �20 ?C for future use. A freshly prepared aqueous solution of ETME of different concentrations was employed into each experiment. The ETME mediated anti-tumor response in Dalton�s lymphoma was evaluated in the inbred populations of BALB/c (H2d) strain of mice of either sex at 8�12 weeks of age. The cytotoxicity of ETME in cancer cells, effects on morphology of cell and nucleus, alteration in the mitochondrial membrane potential, and level of expression of proapoptotic proteins (Bcl-2, cyt C, Bax and p53) were done using known procedures. Results: The ETME contained high content of total alkaloids (96.02 � 3.30 mg/100 mg), flavonoids (15.77 � 2.38 mg/100 mg), carbohydrate (12.71 � 0.59 mg/100 mg), ascorbic acid (12.48 � 2.59 mg/100 mg), and phenolics (0.94 � 0.05 mg/100 mg). Gas chromatography-mass spectrometry (GC-MS) analysis indicated the presence of 23 phytochemicals with known anticancer properties. DL cells treated with ETME exhibited significant and concentration dependent cytotoxicity. Florescent microscopy and flow cytometry of ETME treated DL cells indicated significant repair in cellular morphology and decreased mitochondrial potential, respectively. Western blot analysis displayed up-regulation of proapoptotic proteins (Bax, Cyt-c, p53) and down regulation of anti-apoptotic protein (Bcl2) in DL cells treated with ETME. Conclusions: The findings of this study clearly indicated that the anticancer property of ETME was mediated via reduction in mitochondrial potential and induction of apoptotic mechanism. Further studies are warranted to explore the anticancer activities of active ingredients present in this microalga of pharmaceutical importance. Copyright: � 2022 The Author(s).Publication Putative role of natural products as Protein Kinase C modulator in different disease conditions(Springer Science and Business Media Deutschland GmbH, 2021) Singh, Rishi Kant; Kumar, Sanjay; Tomar, Munendra Singh; Verma, Praveen Kumar; Kumar, Amit; Kumar, Sandeep; Kumar, Naveen; Singh, Jai Prakash; Acharya, ArbindIntroduction: Protein kinase C (PKC) is a promising drug target for various therapeutic areas. Natural products derived from plants, animals, microorganisms, and marine organisms have been used by humans as medicine from prehistoric times. Recently, several compounds derived from plants have been found to modulate PKC activities through competitive binding with ATP binding site, and other allosteric regions of PKC. As a result fresh race has been started in academia and pharmaceutical companies to develop an effective naturally derived small-molecule inhibitor to target PKC activities. Herein, in this review, we have discussed several natural products and their derivatives, which are reported to have an impact on PKC signaling cascade. Methods: All information presented in this review article regarding the regulation of PKC by natural products has been acquired by a systematic search of various electronic databases, including ScienceDirect, Scopus, Google Scholar, Web of science, ResearchGate, and PubMed. The keywords PKC, natural products, curcumin, rottlerin, quercetin, ellagic acid, epigallocatechin-3 gallate, ingenol 3 angelate, resveratrol, protocatechuic acid, tannic acid, PKC modulators from marine organism, bryostatin, staurosporine, midostaurin, sangivamycin, and other relevant key words were explored. Results: The natural products and their derivatives including curcumin, rottlerin, quercetin, ellagic acid, epigallocatechin-3 gallate, ingenol 3 angelate, resveratrol, bryostatin, staurosporine, and midostaurin play a major role in the management of PKC activity during various disease progression. Conclusion: Based on the comprehensive literature survey, it could be concluded that various natural products can regulate PKC activity during disease progression. However, extensive research is needed to circumvent the challenge of isoform specific regulation of PKC by natural products. � 2021, Springer Nature Switzerland AG.
