Browsing by Author "Vishal Kumar Gupta"

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Adjunct therapeutic potential of phytochemicals against cancer
(Elsevier, 2019) Vishal Kumar Gupta; Pradip Kumar Jaiswara; Pratishtha Sonker; Shiv Govind Rawat; Ajay Kumar
Cancer is a devastating disease which is responsible for the second major cause of death worldwide. The major factors associated with high death rate by cancer include late diagnosis, severe side effects of conventional anticancer drugs, and complex therapeutic procedures. In recent years, the use of phytochemicals has been exponentially increased in the field of cancer therapeutics because of its wide range of pharmacological values, promising therapeutic efficacy, low cost, and minimal side effects. The adjunct therapeutic potential of phytochemicals has also been tested in laboratory to clinics. Furthermore, the findings of several studies indicate the effective and promising adjunct therapeutic potential of phytochemicals against various cancers which informs the decision to utilize the phytochemicals as adjunct cancer therapeutic agents for designing the novel combinatorial cancer therapeutic approaches for the effective and safer treatment of cancer patients. This chapter is an attempt to discuss the potential adjunct therapeutic values of phytochemicals against cancer. © 2020 Elsevier Inc. All rights reserved.
Assessing the efficacy of nanofabricated plant-based antifungal formulation against the growth and zearalenone toxin production by Fusarium graminearum
(Springer Nature, 2025) Vishal Kumar Gupta; Tanya Singh Raghuvanshi; Vivekanand; Bhanu Prakash
The study investigates the efficacy of nanoencapsulated antifungal formulation (Ne-CIM) against the growth and zearalenone toxin production by Fusarium graminearum with a detailed mechanism of action. Antifungal and zearalenone toxin inhibitory effects of individual essential oils (EOs) (Carum carvi, and Illicium verum), methyl anthranilate, and their combination (CIM; 1:1:0.5) were recorded in terms of minimum inhibitory concentration (MIC) at (0.80, 0.50, 0.70 and 0.50 µl/ml) and (0.60, 0.40, 0.60 and 0.40 µl/ml) respectively. The antifungal formulation CIM was nanoencapsulated inside the chitosan nanogel and characterized using FTIR, DLS, and XRD. The result revealed that Ne-CIM exhibited elevated antifungal and zearalenone toxin inhibition at 0.40 and 0.30 µl/ml respectively which was found to be superior over the individual EOs and mixture formulation. Further, the mechanism of action of Ne-CIM was also explored by targeting the membrane ergosterol, ion leakage, 260/280 absorbing material, antioxidant enzymes, and carbon source utilization level. The result reveals the remarkable impairment in test biochemical parameters over to control. In addition, the practical applicability of Ne-CIM was investigated using in-situ experiments with inoculated toxigenic F. graminearum in raw material from Withania somnifera. The result revealed that at MIC value Ne-CIM protects 70% of fungal growth and 100% of zearalenone toxin, with remarkable protection from lipid peroxidation. The study recommends the Ne-CIM as a novel green antifungal agent for sustainable management of toxigenic F. graminearum. © The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia 2025.
Bioactive lipids: Their synthesis, biological functions and role in diseases
(Nova Science Publisher Inc., 2018) Pradip Jaiswara; Vishal Kumar Gupta; Ajay Kumar
Lipids are one of the major sources of energy and serve as crucial structural components of the cell membrane. In addition, several lipid molecules also play a central role in the regulation of key cellular processes such as survival, proliferation, and growth by interacting with protein binding partners and serving as docking sites for several signaling molecules. Bioactive lipids are usually produced by the metabolism of membrane lipids or from dietary precursor molecules such as amino acids, cholesterol, and fatty acids. Bioactive lipids include lysophosphatidic acid (LPA), sphingosine-1-phosphate (SIP), thromboxanes, prostaglandins and leukotrienes which are derived from phosphatidic acid, lysophosphatidylcholine, sphingosine and arachidonic acid. This book chapter discusses the biosynthetic processes and biological roles of bioactive lipids. © 2018 Nova Science Publishers, Inc.
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 Kumar
In 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. © 2022
Insights of Endocytosis Signaling in Health and Disease
(MDPI, 2023) Chandramani Pathak; Foram U. Vaidya; Bhargav N. Waghela; Pradip Kumar Jaiswara; Vishal Kumar Gupta; Ajay Kumar; Barani Kumar Rajendran; Kishu Ranjan
Endocytosis in mammalian cells is a fundamental cellular machinery that regulates vital physiological processes, such as the absorption of metabolites, release of neurotransmitters, uptake of hormone cellular defense, and delivery of biomolecules across the plasma membrane. A remarkable characteristic of the endocytic machinery is the sequential assembly of the complex proteins at the plasma membrane, followed by internalization and fusion of various biomolecules to different cellular compartments. In all eukaryotic cells, functional characterization of endocytic pathways is based on dynamics of the protein complex and signal transduction modules. To coordinate the assembly and functions of the numerous parts of the endocytic machinery, the endocytic proteins interact significantly within and between the modules. Clathrin-dependent and -independent endocytosis, caveolar pathway, and receptor mediated endocytosis have been attributed to a greater variety of physiological and pathophysiological roles such as, autophagy, metabolism, cell division, apoptosis, cellular defense, and intestinal permeabilization. Notably, any defect or alteration in the endocytic machinery results in the development of pathological consequences associated with human diseases such as cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. In this review, an in-depth endeavor has been made to illustrate the process of endocytosis, and associated mechanisms describing pathological manifestation associated with dysregulated endocytosis machinery. © 2023 by the authors.
Lysophosphatidic acid promotes survival of T lymphoma cells by altering apoptosis and glucose metabolism
(Springer, 2020) Vishal Kumar Gupta; Pradip Kumar Jaiswara; Pratishtha Sonker; Shiv Govind Rawat; Rajan Kumar Tiwari; Ajay Kumar
Lysophosphatidic acid (LPA) is a bioactive lipid, which plays an indispensable role in various physiological and pathological processes. Moreover, an elevated level of LPA has been observed in malignancies of different origins and implicated in their progression via modulation of proliferation, apoptosis, invasion and metastasis. Interestingly, few recent reports suggest a pivotal role of LPA-modulated metabolism in oncogenesis of ovarian cancer. However, little is understood regarding the role of LPA in the development and progression of T cell malignancies, which are considered as one of the most challenging neoplasms for clinical management. Additionally, mechanisms underlying the LPA-dependent modulation of glucose metabolism in T cell lymphoma are also not known. Therefore, the present study was undertaken to explore the role of LPA-altered apoptosis and glucose metabolism on the survival of T lymphoma cells. Observations of this investigation suggest that LPA supports survival of T lymphoma cells via altering apoptosis and glucose metabolism through changing the level of reactive species, namely nitric oxide and reactive oxygen species along with expression of various survival and glucose metabolism regulatory molecules, including hypoxia-inducible factor 1-alpha, p53, Bcl2, and glucose transporter 3, hexokinase II, pyruvate kinase muscle isozyme 2, monocarboxylate transporter 1, pyruvate dehydrogenase kinase 1. Taken together‚ the results of the present investigation decipher the novel mechanisms of LPA-mediated survival of T lymphoma cells via modulation of apoptosis and glucose metabolism. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
Molecular and cellular paradigms of multidrug resistance in cancer
(John Wiley and Sons Inc, 2022) Foram U. Vaidya; Abu Sufiyan Chhipa; Vinita Mishra; Vishal Kumar Gupta; Shiv Govind Rawat; Ajay Kumar; Chandramani Pathak
Background: The acquisition of resistance to chemotherapy is a major hurdle in the successful application of cancer therapy. Several anticancer approaches, including chemotherapies, radiotherapy, surgery and targeted therapies are being employed for the treatment of cancer. However, cancer cells reprogram themselves in multiple ways to evade the effect of these therapies, and over a period of time, the drug becomes inactive due to the development of multi-drug resistance (MDR). MDR is a complex phenomenon where malignant cells become insensitive to anticancer drugs and attain the ability to survive even after several exposures of anticancer drugs. In this review, we have discussed the molecular and cellular paradigms of multidrug resistance in cancer. Recent Findings: An Extensive research in cancer biology revealed that drug resistance in cancer is the result of perpetuated intracellular and extracellular mechanisms such as drug efflux, drug inactivation, drug target alteration, oncogenic mutations, altered DNA damage repair mechanism, inhibition of programmed cell death signaling, metabolic reprogramming, epithelial mesenchymal transition (EMT), inherent cell heterogeneity, epigenetic changes, redox imbalance, or any combination of these mechanisms. An inevitable cross-link between inflammation and drug resistance has been discussed. This review provided insight molecular mechanism to understand the vulnerabilities of cancer cells to develop drug resistance. Conclusion: MDR is an outcome of interplays between multiple intricate pathways responsible for the inactivation of drug and development of resistance. MDR is a major obstacle in regimens of successful application of anti-cancer therapy. An improved understanding of the molecular mechanism of multi drug resistance and cellular reprogramming can provide a promising opportunity to combat drug resistance in cancer and intensify anti-cancer therapy for the upcoming future. © 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC.
Nimbolide induces cell death in T lymphoma cells: Implication of altered apoptosis and glucose metabolism
(John Wiley and Sons Inc, 2021) Pradip Kumar Jaiswara; Vishal Kumar Gupta; Pratishtha Sonker; Shiv Govind Rawat; Rajan Kumar Tiwari; Chandramani Pathak; Santosh Kumar; Ajay Kumar
Nimbolide is a tetranortriterpenoid derived from the leaves and flowers of Azadirachta indica (Neem). It exhibits anticancer activity against a variety of cancers by modulating various crucial features, including cell proliferation, apoptosis, and invasion and metastasis. More importantly, the cytotoxic effect of nimbolide has also been observed against T cell lymphoma, but the underlying mechanisms are still unexplored. So far, no study has been conducted to observe the effect of nimbolide on cancer cell metabolism. Therefore, the present investigation was designed to explore the molecular mechanisms of the antitumor potential of nimbolide against T cell lymphoma, a neoplastic disorder of thymic origin. In addition, we also unraveled the anti-glycolytic activity of nimbolide against T lymphoma cells with possible molecular mechanisms. Our results showed the cytotoxic action of nimbolide against three different cell lines of T cell lymphoma, namely Dalton's lymphoma, HuT-78, and J6. Nimbolide-induced apoptosis in T lymphoma cells by altering the level of reactive oxygen species, p53, Bcl2, Bax, and cytochrome c, with subsequent cleavage of caspase 3. Remarkably, nimbolide inhibited the expression of hypoxia-inducible factor-1α, glucose transporter 3, hexokinase II, and pyruvate dehydrogenase kinase 1, which led to the suppression of glycolysis with concomitant activation of oxidative phosphorylation. Hence, the results of the present investigation demonstrate that nimbolide exerts tumoricidal activity against T lymphoma cells via augmentation of apoptosis and reversal of altered cell metabolism. Thus, the present study provides a new insight for the therapeutic utilization of nimbolide against T cell lymphoma. © 2020 Wiley Periodicals LLC.
Phosphodiesterase 5 inhibitor sildenafil potentiates the antitumor activity of cisplatin by ROS-mediated apoptosis: a role of deregulated glucose metabolism
(Springer, 2022) Shiv Govind Rawat; Rajan Kumar Tiwari; Pradip Kumar Jaiswara; Vishal Kumar Gupta; Pratishtha Sonker; Naveen Kumar Vishvakarma; Santosh Kumar; Chandramani Pathak; Vibhav Gautam; Ajay Kumar
Cyclic nucleotide phosphodiesterase 5 (PDE5) has been recently identified to play a crucial role in the progression of many cancers. PDE5 promotes tumorigenesis by dysregulating various cellular processes such as proliferation, apoptosis, angiogenesis, and invasion and migration. Interestingly, multiple studies have reported the promising chemosensitizing potential of PDE5 inhibitor sildenafil in breast, colon, prostate, glioma, and lung cancers. However, to date, the chemosensitizing action of sildenafil is not evaluated in T cell lymphoma, a rare and challenging neoplastic disorder. Hence, the present investigation was undertaken to examine the chemosensitizing potential of sildenafil against T cell lymphoma along with elucidation of possible involvement of altered apoptosis and glucose metabolism. The experimental findings of this study showed that sildenafil enhances the cytotoxic ability of cisplatin by apoptosis induction through altering the levels of apoptosis regulatory molecules: Bcl-2, Bax, cytochrome c (Cyt c), cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP). These molecular alterations were possibly driven by sildenafil through reactive oxygen species (ROS). Sildenafil deregulates glucose metabolism by markedly lowering the expression of glycolysis regulatory molecules, namely glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase II (HKII), pyruvate kinase M2 (PKM2), and pyruvate dehydrogenase kinase 1 (PDK1) via suppressing hypoxia-inducible factor 1-alpha (HIF-1α) expression. Hence, sildenafil potentiates the tumor cell killing ability of cisplatin by augmenting ROS production through switching the glucose metabolism from glycolysis to oxidative phosphorylation (OXPHOS). Overall, our study demonstrates that sildenafil might be a promising adjunct therapeutic candidate in designing novel combinatorial chemotherapeutic regimens against T cell lymphoma. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Resveratrol as Anti-Obesity and Anticancer Agent
(Springer Singapore, 2021) Vishal Kumar Gupta; Pratishtha Sonker; Ajay Kumar
Resveratrol is a naturally occurring phytochemical, synthesized against various stress responses like infection, UV radiation, and weather change. It plays an important role in the regulation of various biological processes such as inflammation, cell proliferation, apoptosis, calorie restriction, and lipid deposition. Therefore, it exerts several beneficial effects against many diseases such as cancer, cardiovascular diseases, obesity, and diabetes. The anti-obesity potential of resveratrol depends on its ability to regulate adipogenesis, lipogenesis, and lipolysis. The anti-obesity activity of resveratrol also depends on its ability to improve the obesity-altered gut microbiome composition. Moreover, resveratrol exhibits potent anticancer activity against cancer of different origins by inhibiting various cancer-promoting features, including proliferation, apoptosis evasion, invasion, and migration through modulating various signaling pathways. In addition, the adjunct therapeutic potential of resveratrol has also been reported against many cancers. Overall, in this chapter, we have discussed the updated information regarding the anti-obesity and anticancer properties, and adjunct therapeutic potential of resveratrol against obesity and cancer along with associated mechanisms in detail. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Taylor and Francis Pte Ltd. 2021.
Role of lysophosphatidic acid in the regulation of immune cells and hematological malignancies
(Elsevier Inc., 2025) Vishal Kumar Gupta; Kriti Gupta; Pratishtha Sonker; Manoj Kumar Mishra; Ajay Kumar
Lysophosphatidic acid (LPA), a small bioactive glycerophospholipid, has been reported to play an indispensable role in the regulation of a wide range of cellular processes, including cell proliferation, morphology, differentiation, invasion, migration, and apoptosis. Besides, it has a diverse role in the development, differentiation, migration, and trafficking of immune cells. The role of LPA in the functioning of immune cells, such as macrophages, natural killer cells, T cells, and B cells has been poorly understood and is still a major thrust area for immunological research. Further, accumulating experimental evidence indicates the pro-tumoral action of LPA in various cancers, including hematological malignancies. Hematological malignancies or blood cancers are a group of neoplastic conditions derived from the cells of hematopoietic tissues. LPA is reported to promote the development and progression of cancers of hematological origin through altering apoptosis, invasion and migration, metabolism, and anti-tumor immune response. But still, the mechanistic pathways by which LPA supports the development and progression of hematological malignancies are not well explored. The present review aims to provide an elaborate survey on the role of LPA in the functioning of immune cells and its implication in hematological malignancies. © 2025 Elsevier Inc.
Targeting lysophosphatidic acid receptor with Ki16425 impedes T cell lymphoma progression through apoptosis induction, glycolysis inhibition, and activation of antitumor immune response
(Springer, 2022) Vishal Kumar Gupta; Ajay Kumar
Lysophosphatidic acid (LPA) is a small phospholipid that acts as an extracellular lipid mediator. It promotes cancer progression by altering a wide array of cellular processes, including apoptosis, survival, angiogenesis, invasion, and migration through binding with its cognate receptors. Intriguingly, our previous study showed that in vitro treatment of LPA induced survival of T lymphoma cells. Hence, the present investigation was designed to investigate the antitumor potential of Ki16425, an antagonist of LPA receptors, against T cell lymphoma. Our in vitro results showed inhibition of LPA-mediated survival and metabolic activity of T lymphoma cells by Ki16425. Further, in vivo experimental findings indicated the tumor retarding potential of Ki16425 against T cell lymphoma through apoptosis induction, glycolysis inhibition, and immunoactivation. The administration of Ki16425 triggered apoptosis by down-regulating the expression of Bcl2 and up-regulating p53, Bax, cleaved caspase-3, and Cyt c expression. Further, Ki16425 suppressed glycolytic activity with concomitantly decreased expression of GLUT3 and MCT1. Moreover, we also noticed an elevated level of NO and iNOS in tumor cells after Ki16425 administration which might also be responsible for apoptosis induction and suppressed glycolysis. Additionally, we observed an increased population of total leukocytes, lymphocytes, and monocytes along with increased thymocytes count and IL-2 and IFN-γ levels. Besides, we observed amelioration of tumor-induced kidney and liver damages by Ki16425. Taken together, this is the first study that demonstrates that LPA receptors could be potential future therapeutic targets for designing promising therapeutic strategies against T cell lymphoma. © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Targeting of aerobic glycolysis: An emerging therapeutic approach against colon cancer
(Springer International Publishing, 2021) Pradip Kumar Jaiswara; Vishal Kumar Gupta; Shiv Govind Rawat; Rajan Kumar Tiwari; Pratishtha Sonker; Rajendra Prakash Maurya; Ajay Kumar
Colon cancer is one of the leading causes of cancer-associated deaths in men as well as in women worldwide. Therefore, various researches are being conducted to identify suitable therapeutic targets for designing the safer and effective therapeutic regimens against colon cancer. In view of this, aerobic glycolysis has been identified as one of the prominent and potential therapeutic targets for the treatment of colon cancer. Interestingly, overwhelming reports suggest that not the oxidative phosphorylation (OXPHOS) but rather glycolysis is one of the major sources of energy production in colon cancer even in the presence of sufficient oxygen. Hence, the "Warburg effect" or "aerobic glycolysis" is among the most detectable features in colon cancer which directly or indirectly mediates other hallmark features. This metabolic switch benefits colon cancer in several ways with respect to its development and progression, which include promotion of macromolecular synthesis, evasion of apoptosis, drug resistance, and immunosuppression. In colon cancer, mutations in Wnt, p53, and Ras play a critical role in switching the glucose metabolism from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. Overall, targeting of aerobic glycolysis by synthetic or natural compounds may help in designing the novel therapeutic approaches for the treatment of colon cancer. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021.