Other affiliations: The Feinstein Institute for Medical Research, Gurudas College, North Shore-LIJ Health System
Bio: Santanu Paul is an academic researcher from University of Calcutta. The author has contributed to research in topics: Chronic lymphocytic leukemia & Apoptosis. The author has an hindex of 12, co-authored 45 publications receiving 370 citations. Previous affiliations of Santanu Paul include The Feinstein Institute for Medical Research & Gurudas College.
TL;DR: Biosynthesis of SNP aided by L. majuscula enhanced the antiproliferative activity of leukemic cells as well as the antibacterial activity against P. aeruginosa.
Abstract: Recently, silver nanoparticles (SNPs) have received much attention in nanooncology due to their unique therapeutic properties. The aim of this study was to determine the anticancer activity of biosynthesized SNPs against blood cancer along with their antibacterial property. Here, the cyanobacterial strain, Lyngbya majuscula, was used as successful bio-reagent for SNP production. The healthy growing trichomes were exposed to 9 mM silver nitrate solution in the dark for nanosilver production. The synthesized particles were tested for their nanostructure using UV–vis spectroscopy (absorption maxima at 415 nm) and other methods. Presence of elemental silver and the crystallographic nature of the particles were confirmed by EDAX analysis and XRD, respectively. The surface topography, size, and shape of SNPs were determined by AFM and TEM studies. Smooth-surfaced spherical shaped particles with an ∼20–50-nm size range were produced. The average hydrodynamic diameter and zeta potential value of the produced SNPs were 149 nm and −35.2 mV, respectively, indicating high stability of the particles. The fully characterized SNPs were then tested for their effectiveness as antibacterial agents against the Gram-negative bacterium Pseudomonas aeruginosa. The antiproliferative activity of SNP was also screened against three leukemic cell lines (K562, MOLT-3, and REH) through MTT assay. The SNP synthesized by L. majuscula showed dose- and time-dependent anticancer activity in REH cells. DAPI staining clearly revealed the fragmentation of nuclei of cancer cells due to SNP treatment. Data taken together showed that biosynthesis of SNP aided by L. majuscula enhanced the antiproliferative activity of leukemic cells as well as the antibacterial activity against P. aeruginosa.
TL;DR: This review provides a comprehensive report on Alpinia galanga having anti-proliferative, apoptotic, anti angiogenic as well as cytotoxic efficacy and their mode of action in vitro aswell as in vivo condition.
Abstract: Introduction: From the ancient Vedic era, green plants are being used for their medicinal properties to treat several diseases. Green plants represent a big source of bioactive compounds. Alpinia galanga (Linn.) of Zingiberaceae family is one amongst those medicinally important plants. Different parts of the plant are used in the treatment of many diseases for its anti-fungal, anti-tumour, antimicrobial, anti-inflammatory, anti-diabetic, antioxidant, antiulcer and many other properties. Several active compounds such as 1’S-1’-acetoxychavicol acetate, 1’S-1’-acetoxyeuginol acetate, 1, 8-cineol, α-fenchyl acetate, β-farnesene, β-bisabolene, α-bergamotene, β-pinene, β-Sitosteroldiglucoside (AG-7), β-sitsteryl Arabinoside (AG-8), 1’-acetoxychavicol acetate (galangal acetate), p-hydroxycinnamaldehyde has been extracted from the plant. Methods: Relevant information was collected from scientific journals, books, and reports via electronic search using Medline, PubMed, Science Direct and Scopus. Results: This review provides a comprehensive report on Alpinia galanga having anti-proliferative, apoptotic, anti angiogenic as well as cytotoxic efficacy and their mode of action in vitro as well as in vivo condition. Conclusion: Considering the ability of the golden treasure present in Alpinia galanga, this review is aimed to summarize the information of the chemical constituents, pharmacological and therapeutic effects of the plant.
TL;DR: Data suggest that in vivo structurally diverse epitopes could bind smIgs of distinct CLL clones, thereby altering survival and growth, and peptides that inhibit or alter the consequences of antigen-smIg interactions may represent therapeutic modalities in CLL.
Abstract: Despite a wealth of information about the structure of surface membrane immunoglobulin (smIg) on chronic lymphocytic leukemia (CLL) cells, little is known about epitopes reacting with their binding sites. Probing phage-displayed peptide libraries, we identified and characterized mimetopes for Igs of 4 patients with IGHV mutated CLL (M-CLL) and 4 with IGHV unmutated CLL (U-CLL). Six of these mAbs were representatives of stereotyped B-cell receptors characteristic of CLL. We found that mimetic epitopes for U- and M-CLL Igs differed significantly. M-CLL–derived peptides exhibited better amino acid motifs, were more similar to each other, aligned more easily, and formed tighter clusters than U-CLL–derived peptides. Mono-, oligo-, and polyreactivity of peptides correlated with structural changes within antigen-binding sites of selecting M-CLL mAbs. Although M-CLL–isolated peptides and certain U-CLL mAbs bound more effectively to the selecting mAb, others were not as specific, reacting with M-CLL and U-CLL mAbs; these data suggest that in vivo structurally diverse epitopes could bind smIgs of distinct CLL clones, thereby altering survival and growth. Finally, an M-CLL–derived peptide inhibited, in a dose-dependent manner, binding of its homologous mAb to human B lymphocytes; therefore peptides that inhibit or alter the consequences of antigen-smIg interactions may represent therapeutic modalities in CLL.
TL;DR: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.
Abstract: Background: Curcumin has has been reported to exert anti-inflammatory, anti-oxidation and anti-angiogenic activity in various types of cancer. It has also been shown to induce apoptosis in leukemia cells. We aimed to unravel the role of the redox pathway in Curcumin mediated apoptosis with a panel of human leukemic cells. Materials and Methods: In this study in vitro cytotoxicity of Curcumin was measured by MTT assay and apoptotic effects were assessed by annexin V/PI, DAPI staining, cell cycle analysis, measurement of caspase activity and PARP cleavage. Effects of Curcumin on intracellular redox balance were assessed using fluorescent probes like H 2 DCFDA, JC1 and an ApoGSH Glutathione Detection Kit respectively. Results: Curcumin showed differential anti-proliferative and apoptotic effects on different human leukemic cell lines in contrast to minimal effects on normal cells. Curcumin induced apoptosis was associated with the generation of intracellular ROS, loss of mitochondrial membrane potential, intracellular GSH depletion, caspase activation. Conclusions: As Curcumin induces programmed cell death specifically in leukemic cells it holds a great promise as a future therapeutic agent in the treatment of leukemia.
TL;DR: In this article, the authors compared 1,2,4-trihydroxy-9,10-anthraquinone (THA) with Anthracycline drugs and showed that THA is a suitable substitute for Anthracyline drugs.
Abstract: Anthracycline drugs show anticancer activity, an ability to inhibit DNA replication and RNA transcription but are costly. This study attempts to see if cheaper hydroxy-9,10-anthraquinones (1,2,4-trihydroxy-9,10-anthraquinone) that structurally resemble anthracyclines mimic its biological interactions and whether it can be a suitable substitute. Proton dissociation at 298 K for THA, pK1 = 4.82 ± 0.05 (phenolic OH at C2) and particularly pK2 = 9.22 ± 0.05 (phenolic OH at C1 and C4) closely resemble those of the anthracyclines. THA undergoes a single step two-electron reduction in aqueous media (pH 7.36) having E1/2 = −0.69 V and two successive single-electron reduction in DMF having E1/2 values −0.70 V and −1.06 V, respectively. CV data showed quasi-reversible nature of THA in aqueous media. E1/2 values of THA were comparable to anthracycline drugs suggesting similarity in redox behavior. Binding studies of THA to ct DNA using UV–Vis and fluorescence spectroscopy were analyzed. Intrinsic binding constant and site size of interaction were (4.80 ± 0.2) × 104 M−1 and (5.96 ± 0.3) bases, respectively. THA, approximately three to five times weaker in binding ct DNA than anthracycline anticancer drugs suggests a role for sugar moieties present in anthracyclines. Anti-leukemic activity studies of THA on cultured MOLT-4 cell lines were performed and apoptosis measured by MTT assay. Result indicates THA to be a potent inducer of apoptosis in MOLT-4 cell line having an IC50 value of 33.8 µM. THA therefore possesses anti-leukemic activity that is comparable to anthracyclines on P388 leukemia and the study reveals that 1,2,4-trihydroxy-9,10-anthraquinone to be a suitable substitute to the costlier anthracyclines. Copyright © 2011 John Wiley & Sons, Ltd.
TL;DR: The disruption of tumor microenvironment interactions and the inhibition of BCR signaling as promising therapeutic strategies in CLL are identified.
Abstract: Chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes, involves blood, bone marrow, and secondary lymphoid organs such as the lymph nodes (LN). A role of the tissue microenvironment in the pathogenesis of CLL is hypothesized based on in vitro observations, but its contribution in vivo remains ill-defined. To elucidate the effects of tumor-host interactions in vivo, we purified tumor cells from 24 treatment-naive patients. Samples were obtained concurrently from blood, bone marrow, and/or LN and analyzed by gene expression profiling. We identified the LN as a key site in CLL pathogenesis. CLL cells in the LN showed up-regulation of gene signatures, indicating B-cell receptor (BCR) and nuclear factor-κB activation. Consistent with antigen-dependent BCR signaling and canonical nuclear factor-κB activation, we detected phosphorylation of SYK and IκBα, respectively. Expression of BCR target genes was stronger in clinically more aggressive CLL, indicating more effective BCR signaling in this subtype in vivo. Tumor proliferation, quantified by the expression of the E2F and c-MYC target genes and verified with Ki67 staining by flow cytometry, was highest in the LN and was correlated with clinical disease progression. These data identify the disruption of tumor microenvironment interactions and the inhibition of BCR signaling as promising therapeutic strategies in CLL. This study is registered at http://clinicaltrials.gov as NCT00019370.
TL;DR: The CLL-phenotype cells found in the general population and in subjects with lymphocytosis have features in common with CLL cells.
Abstract: Background A diagnosis of chronic lymphocytic leukemia (CLL) requires a count of over 5000 circulating CLL-phenotype cells per cubic millimeter. Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL. Methods We investigated 1520 subjects who were 62 to 80 years of age with a normal blood count and 2228 subjects with lymphocytosis (>4000 lymphocytes per cubic millimeter) for the presence of MBL, using flow cytometry. Monoclonal B cells were further characterized by means of cytogenetic and molecular analyses. A representative cohort of 185 subjects with CLL-phenotype MBL and lymphocytosis were monitored for a median of 6.7 years (range, 0.2 to 11.8). Results Monoclonal CLL-phenotype B cells were detected in 5.1% of subjects (78 of 1520) with a normal blood count and 13.9% (309 of 2228) with lymphocytosis. CLL-phenotype MBL had a frequency of 13q14 deletion and trisomy 12 similar to that of C...
TL;DR: It is shown that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR.
Abstract: B-cell receptor (BCR) signalling in chronic lymphocytic leukaemia (CLL) is found not to be dependent on exogenous antigens; instead, signalling may involve the binding of the BCR heavy-chain complementarity-determining region to self epitopes on the same receptor, a finding that may have important implications for understanding the pathogenesis of CLL and potential therapeutic approaches. Chronic lymphocytic leukaemia (CLL) is one of the commonest forms of leukaemia in the Western world. B-cell antigen receptor (BCR) expression is a feature of the condition, but it has been unclear whether malignancy is actually driven by BCR signalling, and hence specific antigens. Hassan Jumaa and colleagues now demonstrate that in a subset of human CLL cases, BCR signalling is important, but not dependent on exogenous antigens. Instead, activation involves the binding of one region of the BCR to self epitopes on variable regions of the same receptor. This finding has important implications for both our understanding of the pathogenesis of CLL and potential novel therapeutic approaches. B-cell antigen receptor (BCR) expression is an important feature of chronic lymphocytic leukaemia (CLL), one of the most prevalent B-cell neoplasias in Western countries1. The presence of stereotyped and quasi-identical BCRs in different CLL patients suggests that recognition of specific antigens might drive CLL pathogenesis. Here we show that, in contrast to other B-cell neoplasias, CLL-derived BCRs induce antigen-independent cell-autonomous signalling, which is dependent on the heavy-chain complementarity-determining region (HCDR3) and an internal epitope of the BCR. Indeed, transferring the HCDR3 of a CLL-derived BCR provides autonomous signalling capacity to a non-autonomously active BCR, whereas mutations in the internal epitope abolish this capacity. Because BCR expression was required for the binding of secreted CLL-derived BCRs to target cells, and mutations in the internal epitope reduced this binding, our results indicate a new model for CLL pathogenesis, with cell-autonomous antigen-independent signalling as a crucial pathogenic mechanism.
TL;DR: Synthesized Ag-NPs exhibited strong antibacterial activity against multidrug-resistant bacteria (Escherichia coli and Bacillus cereus) as well as cytotoxic effects against both human breast and human colon cancer cell lines.
Abstract: Using aqueous cyanobacterial extracts in the synthesis of silver nanoparticle is looked as green, ecofriendly, low priced biotechnology that gives advancement over both chemical and physical methods. In the current study, an aqueous extract of Oscillatoria limnetica fresh biomass was used for the green synthesis of Ag-NPs, since O. limnetica extract plays a dual part in both reducing and stabilizing Oscillatoria-silver nanoparticles (O-AgNPs). The UV-Visible absorption spectrum, Fourier transforms infrared (FT-IR), transmission electron microscopy (TEM) and scanning electron microscope (SEM) were achieved for confirming and characterizing the biosynthesized O-AgNPs. TEM images detected the quasi-spherical Ag-NPs shape with diverse size ranged within 3.30–17.97 nm. FT-IR analysis demonstrated the presence of free amino groups in addition to sulfur containing amino acid derivatives acting as stabilizing agents as well as the presence of either sulfur or phosphorus functional groups which possibly attaches silver. In this study, synthesized Ag-NPs exhibited strong antibacterial activity against multidrug-resistant bacteria (Escherichia coli and Bacillus cereus) as well as cytotoxic effects against both human breast (MCF-7) cell line giving IC50 (6.147 µg/ml) and human colon cancer (HCT-116) cell line giving IC50 (5.369 µg/ml). Hemolytic activity of Ag-NPs was investigated and confirmed as being non- toxic to human RBCs in low concentrations.
TL;DR: The review shows the neem has been used by humankind to treat various ailments from prehistory to contemporary.
Abstract: The divine tree neem (Azadirachta indica) is mainly cultivated in the Indian subcontinent. Neem has been used extensively by humankind to treat various ailments before the availability of written records which recorded the beginning of history. The world health organization estimates that 80% of the population living in the developing countries relies exclusively on traditional medicine for their primary health care. More than half of the world's population still relies entirely on plants for medicines, and plants supply the active ingredients of most traditional medical products. The review shows the neem has been used by humankind to treat various ailments from prehistory to contemporary.