Department Of Zoology

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Author: search.filters.author.Kumar, Raj

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    Biodegradable nanoparticulate co-delivery of flavonoid and doxorubicin: Mechanistic exploration and evaluation of anticancer effect in vitro and in vivo
    (Elsevier Ltd, 2021-07-30T00:00:00) Khan, Iliyas; Sarkar, Bibekananda; Joshi, Gaurav; Nakhate, Kartik T.; Ajazuddin; Mantha, Anil K.; Kumar, Raj; Kaul, Ankur; Chaturvedi, Shubhra; Mishra, Anil K.; Gupta, Umesh
    The proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 � 4.27 nm in size, having 0.112 � 0.035 PDI, with -10.1 � 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The in vitro studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition via an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. In vivo studies results revealed better half-life (27.35 � 1.58 and 11.98 � 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. In vivo biodistribution study was also in accordance with the in vitro studies and in line with the in vivo pharmacokinetic. In vivo tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice. � 2021 The Author(s)
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    DNA Repair and Redox Activities and Inhibitors of Apurinic/ Apyrimidinic Endonuclease 1/Redox Effector Factor 1 (APE1/Ref-1): A Comparative Analysis and Their Scope and Limitations toward Anticancer Drug Development
    (ACS Publications, 2014) Kaur, Gagandeep; Cholia, Ravi P.; Mantha, Anil K.; Kumar, Raj
    The apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional enzyme involved in DNA repair and activation of transcription factors through its redox function. The evolutionarily conserved C- and N-termini are involved in these functions independently. It is also reported that the activity of APE1/Ref-1 abruptly increases several-fold in various human cancers. The control over the outcomes of these two functions is emerging as a new strategy to combine enhanced DNA damage and chemotherapy in order to tackle the major hurdle of increased cancer cell growth and proliferation. Studies have targeted these two domains individually for the design and development of inhibitors for APE1/Ref-1. Here, we have made, for the first time, an attempt at a comparative analysis of APE1/Ref-1 inhibitors that target both DNA repair and redox activities simultaneously. We further discuss their scope and limitations with respect to the development of potential anticancer agents.
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    An in vitro study ascertaining the role of H2O2 and glucose oxidase in modulation of antioxidant potential and cancer cell survival mechanisms in glioblastoma U-87 MG cells
    (Springer New York LLC, 2017) Cholia, Ravi P.; Kumari, Sanju; Kumar, Saurabh; Kaur, Manpreet; Kaur, Manbir; Kumar, Raj; Dhiman, Monisha; Mantha, Anil K.
    Glial cells protect themselves from the elevated reactive oxygen species (ROS) via developing unusual mechanisms to maintain the genomic stability, and reprogramming of the cellular antioxidant system to cope with the adverse effects. In the present study non-cytotoxic dose of oxidants, H2O2 (100??M) and GO (10??U/ml) was used to induce moderate oxidative stress via generating ROS in human glioblastoma cell line U-87 MG cells, which showed a marked increase in the antioxidant capacity as studied by measuring the modulation in expression levels and activities of superoxide dismutase (SOD1 and SOD2) and catalase (CAT) enzymes, and the GSH content. However, pretreatment (3?h) of Curcumin and Quercetin (10??M) followed by the treatment of oxidants enhanced the cell survival, and the levels/activities of the antioxidants studied. Oxidative stress also resulted in an increase in the nitrite levels in the culture supernatants, and further analysis by immunocytochemistry showed an increase in iNOS expression. In addition, phytochemical pretreatment decreased the nitrite level in the culture supernatants of oxidatively stressed U-87 MG cells. Elevated ROS also increased the expression of COX-2 and APE1 enzymes and pretreatment of Curcumin and Quercetin decreased COX-2 expression and increased APE1 expression in the oxidatively stressed U-87 MG cells. The immunocytochemistry also indicates for APE1 enhanced stress-dependent subcellular localization to the nuclear compartment, which advocates for enhanced DNA repair and redox functions of APE1 towards survival of U-87 MG cells. It can be concluded that intracellular oxidants activate the key enzymes involved in antioxidant mechanisms, NO-dependent survival mechanisms, and also in the DNA repair pathways for glial cell survival in oxidative-stress micro-environment. ? 2017, Springer Science+Business Media, LLC.