Browsing by Author "Soni, Vivek Kumar"

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    Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells
    (Frontiers Media S.A., 2021) Soni, Vivek Kumar; Mehta, Arundhati; Ratre, Yashwant Kumar; Chandra, Vikas; Shukla, Dhananjay; Kumar, Ajay; Vishvakarma, Naveen Kumar
    Along with direct anticancer activity, curcumin hinders the onset of chemoresistance. Among many, high glucose condition is a key driving factor for chemoresistance. However, the ability of curcumin remains unexplored against high glucose-induced chemoresistance. Moreover, chemoresistance is major hindrance in effective clinical management of liver cancer. Using hepatic carcinoma HepG2 cells, the present investigation demonstrates that high glucose induces chemoresistance, which is averted by the simultaneous presence of curcumin. Curcumin obviated the hyperglycemia-induced modulations like elevated glucose consumption, lactate production, and extracellular acidification, and diminished nitric oxide and reactive oxygen species (ROS) production. Modulated molecular regulators are suggested to play a crucial role as curcumin pretreatment also prevented the onset of chemoresistance by high glucose. High glucose instigated suppression in the intracellular accumulation of anticancer drug doxorubicin and drug-induced chromatin compactness along with declined expression of drug efflux pump MDR-1 and transcription factors and signal transducers governing the survival, aggressiveness, and apoptotic cell death (p53, HIF-1?, mTOR, MYC, STAT3). Curcumin alleviated the suppression of drug retention and nuclear condensation along with hindering the high glucose-induced alterations in transcription factors and signal transducers. High glucose-driven resistance in cancer cells was associated with elevated expression of metabolic enzymes HKII, PFK1, GAPDH, PKM2, LDH-A, IDH3A, and FASN. Metabolite transporters and receptors (GLUT-1, MCT-1, MCT-4, and HCAR-1) were also found upregulated in high glucose exposed HepG2 cells. Curcumin inhibited the elevated expression of these enzymes, transporters, and receptors in cancer cells. Curcumin also uplifted the SDH expression, which was inhibited in high glucose condition. Taken together, the findings of the present investigation first time demonstrate the ability of curcumin against high glucose-induced chemoresistance, along with its molecular mechanism. This will have implication in therapeutic management of malignancies in diabetic conditions. � Copyright � 2021 Soni, Mehta, Ratre, Chandra, Shukla, Kumar and Vishvakarma.
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    Curcumin: a spice pigment against hepatic cancer
    (Elsevier, 2022) Soni, Vivek Kumar; Ratre, Yashwant Kumar; Mehta, Arundhati; Dixit, Ashwini Kumar; Dwivedi, Mrigendra; Shukla, Dhananjay; Kumar, Ajay; Vishvakarma, Naveen Kumar
    Hepatic cancer is one of the most deadly malignancies owing to the pivotal role of liver in physiological homeostasis. Various strategies are being implemented to combat the onset and progression of liver cancer that has achieved promising success. However, conventional therapeutic approaches have their own limitations, particularly nonspecific toxicity and the onset of the chemoresistance. Therefore alternative approaches, including bioactive components of natural origins are being explored for their antineoplastic activity. Curcumin, the yellow pigment of turmeric spice, has shown effective cytotoxic activity against numerous malignant cells, including hepatic cancer. The abilities of curcumin such as its antioxidant nature, antiinflammatory effects, immunostimulatory activity, and protective behavior against organ damage make this phytochemical as a better choice of therapeutic agent in various medical ailments including malignancies of hepatic origin. Mechanistic explorations on curcumin have identified various molecular targets for its therapeutic effects against liver cancer. Moreover, curcumin is devoid of any specific adverse effects and safe for consumption. Curcumin also exhibits chemosensitizing ability and makes liver cancer cells more susceptible to conventional chemotherapeutic drugs. Although few concerns, including bioavailability and its metabolism limit the optimal clinical exploitation of curcumin, its derivatives is found to overcome such obstacles. Collectively curcumin stands high in prospective therapeutic molecules against liver cancers with evident success in preclinical as well clinical investigations. � 2022 Elsevier Inc. All rights reserved.
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    Orchestral role of lipid metabolic reprogramming in T-cell malignancy
    (Frontiers Media S.A., 2023) Mehta, Arundhati; Ratre, Yashwant Kumar; Soni, Vivek Kumar; Shukla, Dhananjay; Sonkar, Subhash C.; Kumar, Ajay; Vishvakarma, Naveen Kumar
    The immune function of normal T cells partially depends on the maneuvering of lipid metabolism through various stages and subsets. Interestingly, T-cell malignancies also reprogram their lipid metabolism to fulfill bioenergetic demand for rapid division. The rewiring of lipid metabolism in T-cell malignancies not only provides survival benefits but also contributes to their stemness, invasion, metastasis, and angiogenesis. Owing to distinctive lipid metabolic programming in T-cell cancer, quantitative, qualitative, and spatial enrichment of specific lipid molecules occur. The formation of lipid rafts rich in cholesterol confers physical strength and sustains survival signals. The accumulation of lipids through de novo synthesis and uptake of free lipids contribute to the bioenergetic reserve required for robust demand during migration and metastasis. Lipid storage in cells leads to the formation of specialized structures known as lipid droplets. The inimitable changes in fatty acid synthesis (FAS) and fatty acid oxidation (FAO) are in dynamic balance in T-cell malignancies. FAO fuels the molecular pumps causing chemoresistance, while FAS offers structural and signaling lipids for rapid division. Lipid metabolism in T-cell cancer provides molecules having immunosuppressive abilities. Moreover, the distinctive composition of membrane lipids has implications for immune evasion by malignant cells of T-cell origin. Lipid droplets and lipid rafts are contributors to maintaining hallmarks of cancer in malignancies of T cells. In preclinical settings, molecular targeting of lipid metabolism in T-cell cancer potentiates the antitumor immunity and chemotherapeutic response. Thus, the direct and adjunct benefit of lipid metabolic targeting is expected to improve the clinical management of T-cell malignancies. Copyright � 2023 Mehta, Ratre, Soni, Shukla, Sonkar, Kumar and Vishvakarma.