Biology subjects

Mohanty, A.

Publications and source records attributed to Mohanty, A..

24 records · Page 2Linked to original sources

bioRxiv2022

Deciphering therapeutic efficacy of mycosynthesized silver nanoparticles using entomopathogenic fungi Metarhizium anisopliae against MCF-7 breast cancer cells in vitro

Green synthesis of silver nanoparticles has gained much interest over few decades in the field of biomedical research due to their ease of synthesis, cost effectiveness, enhanced bioactivity and biocompatibility compared to the chemical synthesis. Recent studies on silver nanoparticles have shown their potential in various fields like antimicrobial, anticancer, larvicidal, catalytic, and wound healing properties. In the present study, entomopathogenic fungi Metarhizium anisopliae was used to synthesize silver nanoparticles. These silver nanoparticles were synthesized and characterized using UV-Vis spectroscopy, FESEM, FETEM and FTIR. Compared to the chemically synthesized silver nanoparticles, the mycosynthesized silver nanoparticles (MaAgNP) showed high yield. The size of mycosynthesized silver nanoparticles was found to be 5-20 nm and was spherical in shape. FTIR results confirmed the possible functional groups that are responsible for the reduction of silver ions. The mycosynthesized silver nanoparticles showed cytotoxicity on human breast cancer cell line (MCF-7) and the calculated IC50 value for MaAgNP was found to be 16.50 g ml-1 whereas the chemically synthesized silver nanoparticles showed cytotoxicity but with increasing concentration, no further significant reduction in cell viability was observed. The possible reason behind improved cytotoxicity of MaAgNP can be the presence of extracellular secondary metabolites present in the fungal filtrate used to synthesize the nanoparticles. The MaAgNP was also observed to induce cell death through reactive oxygen species (ROS) generation.

cancer biology↗

bioRxiv2021

Knockdown of a novel ATPase domain of capsid protein inhibits genome packaging in potato leaf roll virus

Potato leaf roll virus (PLRV) uses powerful molecular machines to package its genome into a viral capsid employing ATP as fuel. Although, recent bioinformatics and structural studies have revealed detailed mechanism of DNA packaging, little is known about the mechanochemistry of genome packaging in small plant viruses such as PLRV. We have identified a novel P-loop-containing ATPase domain with two Walker A-like motifs, two arginine fingers, and two sensor motifs distributed throughout the polypeptide chain of PLRV capsid protein (CP). The composition and arrangement of the ATP binding and hydrolysis domain of PLRV CP is unique and rarely reported. The discovery of the system sheds new light on the mechanism of viral genome packaging, regulation of viral assembly process, and evolution of plant viruses. Here, we used the RNAi approach to suppress CP gene expression, which in turn prevented PLRV genome packaging and assembly in Solanum tuberosum cv. Khufri Ashoka. Potato plants agroinfiltrated with siRNA constructs against the ATPase domain of CP exhibited no rolling symptoms upon PLRV infection, indicating that the silencing of CP gene expression is an efficient method for generating PLRV-resistant potato plants. Moreover, our findings provide a robust approach to generate PLRV-resistant potato plants, which can be further extended to other species. Finally, we propose a new mechanism of genome packaging and assembly in plant viruses.

molecular biology↗

bioRxiv2020

The Ephrin receptor A2 and Roundabout Guidance Receptor 1 heterodimer: A potential theranostic for squamous cell carcinomas

Squamous cell carcinomas (SCC) of the lung (LSCC) and head and neck (HNSCC) are very prevalent with poor prognosis and limited treatment options. In both cancer types, Ephrin receptor A2 (EPHA2) is known to be overexpressed and exhibit opposing effects via two distinct signaling mechanisms. While it can inhibit cancer cell survival and migration by ligand-dependent signaling through tyrosine kinase phosphorylation at Y588 and Y772, it can promote tumor progression and cell migration in a ligand-independent manner via phosphorylation at S897. Variable ABnormal morphology (VAB-1) is the C. elegans ortholog of the human ephrin receptor (EPHR) that interacts genetically and biochemically in a dose-dependent manner with the axon guidance receptor, SAX3, the worm ortholog of ROBO. Double mutants of vab-1(EPHR)/sx-3(ROBO) are synthetic lethal, underscoring the interaction between the two signaling pathways which prompted us to investigate their role in SCC. Using biochemical and biophysical techniques, we show that EPHA2 and ROBO1 reside in the same complex and interact physically to form a functional heterodimer in LSCC and HNSCC. Furthermore, we show that treating squamous cells with the SLIT2, ligand of ROBO1, hinders phosphorylation of EPHA2 at S897, and thereby, attenuates cell proliferation. Interestingly, SLIT2 can interact with EPHA2 and attenuate the proliferation of cells that have low ROBO1 expression. Additionally, SLIT2 can act synergistically with the EPHA2 inhibitor, Ensartinib to attenuate cell growth in LSCC and HNSCC cells. Taken together, the data suggest that SLIT2 may serve as a novel therapeutic for LSCC and HNSCC. Here, we propose to stratify patients for treatment with SLIT2 and/or Ensartinib, based on their EPHA2 and ROBO1 expression levels in the diseased tissue. Thus 85% of LSCC cases can be treated with combination of SLIT2+Ensartinib and 55% of HNSCC cases can be treated with either SLIT2 or Ensartinib. Furthermore, EPHA2 and ROBO1 may represent novel theranostics in these two diseases. One sentence summaryHeterodimerization of EPHA2 and ROBO1 receptors attenuates growth of squamous cell carcinomas of the lung and head and neck.

cancer biology↗

bioRxiv2020

Phenotypic switching and adaptive strategies of cancer cells in response to stress: insights from live cell imaging and mathematical modeling

A major challenge in cancer therapy is drug resistance, which is typically attributed to acquired mutations and tumor heterogeneity. However, emerging evidence suggests that dynamic cellular interactions and group behavior also contribute to drug resistance, although, the details of such mechanisms are poorly understood. Here, by combining real time cellular growth data with mathematical modeling, we showed that the cisplatin-sensitive and tolerant lung cancer cells when co-cultured in cisplatin-free and cisplatin-treated environments, exhibit drastically different group strategies in response to environmental changes. While tolerant cells exhibited a persister-like behaviour and were attenuated by sensitive cells, sensitive cells learned to evade chemotherapy from tolerant cells when co-cultured. Further, tolerant cells could switch phenotypes to become sensitive, although high cisplatin concentrations suppressed this switching. Finally, switching cisplatin administration from continuous to intermittent suppressed the emergence of tolerant cells, suggesting that intermittent rather than continuous chemotherapy may result in better outcomes in lung cancer.

cancer biology↗

bioRxiv2019

A Non-genetic Mechanism for Chemoresistance in Lung Cancer: The Role of Integrin β4/Paxillin Axis

Tumor heterogeneity and cisplatin resistance are a major cause of tumor relapse and poor survival. Here we show that in lung adenocarcinoma (LUAD), paxillin (PXN) and integrin beta 4 (ITGB4) are associated with tumor progression, and cisplatin resistance. Silencing PXN and ITGB4 render cisplatin tolerant cells sensitive, and immunologically neutralizing ITGB4 improves sensitivity. The N-terminal half of PXN is intrinsically disordered and interacts with ITGB4 to regulate expression of USP1 and VDAC1 which are required for maintaining genomic stability and mitochondrial function in LUAD. By virtual screening an FDA-approved compound library, we identified compounds that interact with PXN in silico and attenuate cisplatin resistance in LUAD cells. RNAseq analysis identified a double negative feedback loop between ITGB4 and microRNA miR-1-3p, suggesting that bistability could lead to stochastic switching between cisplatin-sensitive and resistant states in these cells. The data highlight an alternate, non-genetic, mechanism underlying chemoresistance in lung cancer.

cancer biology↗

bioRxiv2018

Euchromatic histone methyltransferases regulate peripheral heterochromatin tethering via histone and non-histone protein methylations

Euchromatic histone methyltransferases (EHMTs), members of the KMT1 family, methylate histone and non-histone proteins. Here we uncover a novel role for EHMTs in regulating heterochromatin anchorage to the nuclear periphery (NP) via non-histone (LaminB1) methylations. We show that EHMTs methylates and stabilizes LaminB1 (LMNB1), which associates with the H3K9me2-marked peripheral heterochromatin. Loss of LMNB1 methylation or EHMTs abrogates the heterochromatin anchorage from the NP. We further demonstrate that the loss of EHMTs induces many hallmarks of aging including global reduction of H3K27methyl marks along with altered nuclear-morphology. Consistent with this, we observed a gradual depletion of EHMTs, which correlates with loss of methylated LMNB1 and peripheral heterochromatin in aging human fibroblasts. Restoration of EHMT expression reverts peripheral heterochromatin defect in aged cells. Collectively our work elucidates a new mechanism by which EHMTs regulate heterochromatin domain organization and reveals their impact on fundamental changes associated with the intrinsic aging process.

genetics↗