Browsing by Author "Subash Chandra Gupta"

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A colorimetric and ‘OFF-ON’ fluorometric chemosensor based on a rhodamine-pyrazole derivative for the detection of Al3+, Fe3+and Cr3+metal ions, and its intracellular application
(Royal Society of Chemistry, 2023) Sarita Gond; Pranjalee Yadav; Aayoosh Singh; Somenath Garai; Anusmita Shekher; Subash Chandra Gupta; Vinod P. Singh
The colorimetric and fluorescence responses of a new rhodamine-functionalized probe (E)-2-(((5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)amino)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one (RMP) are investigated. RMP has been thoroughly characterized using various spectroscopic tools and single crystal X-ray diffraction. Among different competing cations, it shows highly sensitive colorimetric and “OFF-ON” fluorescence responses towards Al3+, Fe3+and Cr3+metal ions. The spectral shifts are clearly noticeable in the visible region of the absorption spectrum and can be observed with the naked eye. Fluorescence quantum yield, stoichiometric ratio, binding constant and detection limit of RMP towards Al3+, Fe3+and Cr3+metal ions have been calculated. Furthermore, RMP-M3+ complexes are reversible and sensitive to EDTA, which effectively mimics a molecular logic gate. Al3+, Fe3+and Cr3+metal ions have been further applied in intracellular application in model human cells. © 2023 The Royal Society of Chemistry
A multifunctional basic pH indicator probe for distinguishable detection of Co2+, Cu2+ and Zn2+ with its utility in mitotracking and monitoring cytoplasmic viscosity in apoptotic cells
(Royal Society of Chemistry, 2022) Pranjalee Yadav; Sarita Gond; Anusmita Shekher; Subash Chandra Gupta; Udai P. Singh; Vinod P. Singh
Metal ions such as Co2+, Cu2+ and Zn2+ have extensive applications in biological and industrial realms, but the toxicity caused by these ions poses a serious threat to mankind. However, there is no report in the literature on the development of a chemosensor for distinguishable detection of these toxic ions. Addressing this challenge, a multifunctional probe as a basic pH indicator with both colorimetric and fluorescence turn-on responses has been reported. The probe selectively discriminates Co2+, Cu2+ and Zn2+ ions with brown, dark yellow and greenish yellow colors, respectively, in DMF : water (9 : 1 v/v, HEPES 10 mM). Additionally, a fluorescence turn-on response specific to Zn2+ has also been observed. The sensing mechanism has been explored using UV-Vis, fluorescence spectroscopy and 1H NMR titration and confirmed with computational results. The inhibition of C 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 N isomerization and excited state intramolecular proton transfer (ESIPT) along with chelation enhanced fluorescence emission (CHEF) result in fluorescence enhancement with Zn2+. Job's plot and HRMS spectra confirm a 1 : 1 (L : M) stoichiometry between the probe and metal ions. The probe is able to exhibit excellent viscochromism in DMF : glycerol medium. Live cell imaging on SiHa cells has been successfully performed for intra-cellular detection of Zn2+ at basic pH. Furthermore, the probe displays its utility in mitotracking and monitoring cytoplasmic viscosity changes in SiHa cells. It is efficiently used to recognize the apoptosis process by displaying an enhancement in fluorescence intensity from cancerous SiHa cells to apoptotic cells. © 2022 The Royal Society of Chemistry.
A viscochromic, mechanochromic, and unsymmetrical azine for selective detection of Al3+ and Cu2+ ions and its mitotracking studies
(Royal Society of Chemistry, 2019) Richa Yadav; Abhishek Rai; Avinash Kumar Sonkar; Vipin Rai; Subash Chandra Gupta; Lallan Mishra
A hydrazone obtained by the reaction of 2-hydroxynaphthaldehyde with hydrazine hydrate was allowed to react further with 4-diethylamino-2-hdroxybenzaldehyde to provide an unsymmetrical azine derivative (NDEA). The azine has been characterized using spectroscopic techniques and single crystal X-ray crystallography. It selectively detects Al3+ and Cu2+ ions in aqueous methanol (DMSO:H2O:MeOH = 0.1:1.9:8.0, v/v, HEPES buffer, pH 7.4) and exhibits naked eye visible color changes from greenish yellow to bright yellow and brown on the addition of Al3+ and Cu2+ ions, respectively, with concomitant changes in their absorption spectra. The corresponding solutions containing Al3+ and Cu2+ ions also display changes in their emission spectra via "TURN ON" and "TURN OFF" pathways with a detection limit of 1.65 × 10-7 M and 1.52 × 10-7 M, respectively. NDEA works as a reversible probe towards Al3+ ions and Cu2+ ions by the addition of F- ions and EDTA2- ions, respectively. The complexes of NDEA, separately with Al3+ and Cu2+ ions, have been optimized by DFT (density functional theory). It also exhibits viscochromic and mechanochromic properties. Most importantly, NDEA significantly detects these ions in rat C6 glioma cell lines and displays good cell permeability. It also co-localizes with the commercially available Mitotracker Red and exhibits a unique application as a live cell mitochondrial tracker. Practically, NDEA detects Al3+ and Cu2+ ions in real water samples and blood serum with a high accuracy. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
All edible materials derived biocompatible and biodegradable triboelectric nanogenerator
(Elsevier Ltd, 2019) Gaurav Khandelwal; Tarun Minocha; Sanjeev Kumar Yadav; Arunkumar Chandrasekhar; Nirmal Prashanth Maria Joseph Raj; Subash Chandra Gupta; Sang-Jae Kim
The energy crisis and plastic pollution are of growing concern worldwide. Nanogenerators converting mechanical energy to electrical energy would be of assistance. Triboelectric nanogenerators (TENGs) are inexpensive, simple to fabricate, and afford high output, as revealed by extensive research over the past decade. However, most TENGs use a polymer as either the substrate or the active layer, contributing to plastic pollution. Biodegradable/edible devices are required; they are harmless when discarded. We here derive a single-electrode lightweight TENG (E-TENG) using only edible materials. Laver coated with an edible silver leaf serves as the active layer and a rice sheet as the substrate. We analyzed surface potential, morphology, and roughness; laver was triboelectrically active. The results of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, cell imaging, and 4′,6-diamidino-2-phenylindole (DAPI) staining suggest that the device minimally affected cell viability. The device was bioresorbable in phosphate-buffered saline (PBS) and gastric acid. Output performance was tested using paper, tissue paper, polyvinyl chloride (PVC), and fluorinated ethylene propylene (FEP). The electrical performance was systematically studied; an FEP-laver E-TENG performed best (output of 23 V and current of 315 nA). The output was used to power a hygrometer, a wristwatch, green light-emitting diodes (LEDs), and ultraviolet (UV) LEDs. © 2019 Elsevier Ltd
Association of altered metabolic profiles and long non-coding RNAs expression with disease severity in breast cancer patients: analysis by 1H NMR spectroscopy and RT-q-PCR
(Springer, 2023) Anusmita Shekher; Puneet; Nikee Awasthee; Umesh Kumar; Ritu Raj; Dinesh Kumar; Subash Chandra Gupta
Introduction: Globally, one of the major causes of cancer related deaths in women is breast cancer. Although metabolic pattern is altered in cancer patients, robust metabolic biomarkers with a potential to improve the screening and disease monitoring are lacking. A complete metabolome profiling of breast cancer patients may lead to the identification of diagnostic/prognostic markers and potential targets. Objectives: The aim of this study was to analyze the metabolic profile in the serum from 43 breast cancer patients and 13 healthy individuals. Materials & methods: We used 1H NMR spectroscopy for the identification and quantification of metabolites. q-RT-PCR was used to examine the relative expression of lncRNAs. Results: Metabolites such as amino acids, lipids, membrane metabolites, lipoproteins, and energy metabolites were observed in the serum from both patients and healthy individuals. Using unsupervised PCA, supervised PLS-DA, supervised OPLS-DA, and random forest classification, we observed that more than 25 metabolites were altered in the breast cancer patients. Metabolites with AUC value > 0.9 were selected for further analysis that revealed significant elevation of lactate, LPR and glycerol, while the level of glucose, succinate, and isobutyrate was reduced in breast cancer patients in comparison to healthy control. The level of these metabolites (except LPR) was altered in advanced-stage breast cancer patients in comparison to early-stage breast cancer patients. The altered metabolites were also associated with over 25 signaling pathways related to metabolism. Further, lncRNAs such as H19, MEG3 and GAS5 were dysregulated in the breast tumor tissue in comparison to normal adjacent tissue. Conclusion: The study provides insights into metabolic alteration in breast cancer patients. It also provides an avenue to examine the association of lncRNAs with metabolic patterns in patients. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Biogenic synthesis and characterization of selenium nanoparticles and their applications with special reference to antibacterial, antioxidant, anticancer and photocatalytic activity
(Springer Science and Business Media Deutschland GmbH, 2021) Shraddha Pandey; Nikee Awasthee; Anusmita Shekher; Lal Chand Rai; Subash Chandra Gupta; Santosh Kumar Dubey
Oxyanions of selenium, selenite (SeO3)2− and selenate (SeO4)2− are toxic to terrestrial and aquatic biota but few microorganisms including cyanobacteria are resistant to high levels of selenite. Cyanobacteria evade selenite toxicity through bioreduction and synthesis of selenium nanoparticles (SeNPs). In this study, extracellular biosynthesis of SeNPs (Se0) using cyanobacterium, Anabaena sp. PCC 7120 on exposure to sodium selenite and characterization was done by using UV–visible spectroscopy, SEM–EDX, TEM and FTIR analyses which confirmed spherical shape with size range of 5–50 nm diameter. These biogenic SeNPs demonstrated significant antibacterial and anti-biofilm activity against bacterial pathogens. Furthermore, these SeNPs showed high antioxidant activity at minimum concentration of 50 µg/mL and significant anti-proliferative activity against HeLa cell line with IC50 value of 5.5 µg/mL. The SeNPs also induced accumulation of cancer cells in the sub-G1 phase which was clearly observed in cellular and nuclear morphology. These biofabricated SeNPs also reduced and decolorized toxic methylene blue dye significantly through photocatalytic degradation. Therefore Anabaena sp. PCC 7120 may be employed as a green bioresource to synthesize SeNPs with potential applications in medicine and environmental bioremediation. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Caffeine-enhanced anti-tumor immune response through decreased expression of PD1 on infiltrated cytotoxic T lymphocytes
(Elsevier B.V., 2019) Gullanki Naga Venkata Charan Tej; Kaushik Neogi; Sumit Singh Verma; Subash Chandra Gupta; Prasanta Kumar Nayak
Caffeine (1,3,7-trimethylxanthine) is a naturally occurring, habitually consumed food constituent throughout the world. Prospective cohort studies revealed that caffeine consumption reduces the relative risk of various cancers. Avoiding immune destruction is one of the emerging hallmarks of cancer. One of the immunosuppressive pathways that contribute in avoiding immune destruction by cancer cells is adenosine-A2A receptor pathway. Based on prospective epidemiological and mechanistic preclinical studies of caffeine and its predominant antagonistic effect on A2A receptor, we aimed to investigate the effect of caffeine on T cell infiltration into the tumor and expression of PD-1 receptor on T lymphocytes during tumor initiation and progression in a carcinogen-induced tumor model. Our results demonstrate that caffeine treatment significantly lowered tumor incidence and tumor growth rate. We found that the total T-lymphocyte infiltration and CD8+ T lymphocyte infiltration was significantly increased in caffeine-treated groups. On the other hand, the infiltration of CD4+CD25+ regulatory T lymphocyte was significantly decreased in caffeine-treated groups. In addition, the PD-1 expression on CD8+ T lymphocytes and CD4+CD25+ regulatory T lymphocytes was significantly reduced in caffeine-treated groups. We further investigated whether the observed anti-tumor effect of caffeine is mediated through the release of cytokines. We found that TNF-α and IFN-γ levels were significantly higher in caffeine-treated groups. The findings of the present study unraveled the immune-related mechanisms behind the caffeinated coffee consumption and lower tumor incidence in humans. In conclusion, the blockade of adenosine pathway by caffeine may constitute an effective means to enhance anti-tumor immune response. © 2019
Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back
(Elsevier Ltd, 2016) Amarish Kumar Yadav; Saripella Srikrishna; Subash Chandra Gupta
The fruit fly Drosophila melanogaster has been used for modeling cancer and as an in vivo tool for the validation and/or development of cancer therapeutics. The impetus for the use of Drosophila in cancer research stems from the high conservation of its signaling pathways, lower genetic redundancy, short life cycle, genetic amenability, and ease of maintenance. Several cell signaling pathways in Drosophila have been used for cancer drug development. The efficacy of combination therapy and uptake/bioavailability of drugs have also been studied. Drosophila has been validated using several FDA-approved drugs, suggesting a potential application of this model in drug repurposing. The model is emerging as a powerful tool for high-throughput screening and should significantly reduce the cost and time associated with drug development. In this review we discuss the applications of Drosophila in cancer drug development. The advantages and limitations of the model are discussed. © 2016 Elsevier Ltd
Chronic diseases, inflammation, and spices: How are they linked?
(BioMed Central Ltd., 2018) Ajaikumar B. Kunnumakkara; Bethsebie L. Sailo; Kishore Banik; Choudhary Harsha; Sahdeo Prasad; Subash Chandra Gupta; Alok Chandra Bharti; Bharat B. Aggarwal
Extensive research within the last several decades has revealed that the major risk factors for most chronic diseases are infections, obesity, alcohol, tobacco, radiation, environmental pollutants, and diet. It is now well established that these factors induce chronic diseases through induction of inflammation. However, inflammation could be either acute or chronic. Acute inflammation persists for a short duration and is the host defense against infections and allergens, whereas the chronic inflammation persists for a long time and leads to many chronic diseases including cancer, cardiovascular diseases, neurodegenerative diseases, respiratory diseases, etc. Numerous lines of evidence suggest that the aforementioned risk factors induced cancer through chronic inflammation. First, transcription factors NF-ΚB and STAT3 that regulate expression of inflammatory gene products, have been found to be constitutively active in most cancers; second, chronic inflammation such as pancreatitis, prostatitis, hepatitis etc. leads to cancers; third, activation of NF-ΚB and STAT3 leads to cancer cell proliferation, survival, invasion, angiogenesis and metastasis; fourth, activation of NF-ΚB and STAT3 leads to resistance to chemotherapy and radiation, and hypoxia and acidic conditions activate these transcription factors. Therefore, targeting these pathways may provide opportunities for both prevention and treatment of cancer and other chronic diseases. We will discuss in this review the potential of various dietary agents such as spices and its components in the suppression of inflammatory pathways and their roles in the prevention and therapy of cancer and other chronic diseases. In fact, epidemiological studies do indicate that cancer incidence in countries such as India where spices are consumed daily is much lower (94/100,000) than those where spices are not consumed such as United States (318/100,000), suggesting the potential role of spices in cancer prevention. © 2018 The Author(s).
Clinical Applications of Noncoding RNAs in Cancer
(Elsevier, 2022) Subash Chandra Gupta; Kishore B. Challagundla
Clinical Applications of Noncoding RNAs in Cancer summarizes the existing strategies, advances, and future opportunities on the role of noncoding RNAs in cancer patients. Established clinicians and researchers from all around the world share their views and expertise and provide readers with invaluable knowledge on the subject. This book provides a comprehensive collection of information on the utility of noncoding RNAs in the diagnosis, prognosis, and therapy of cancer. It also discusses the evolutionary significance of noncoding RNAs and how the molecular tools such as RNA-seq, RNA-FISH, ic-SHAPE, and quantitative real-time PCR help in the detection and elucidation of the functions of noncoding RNAs. Additionally, the challenges associated with noncoding RNA approaches and future developments are discussed. It is a valuable resource for cancer researchers, oncologists, clinicians, and other biomedical field members who want to learn more about noninvasive ways to diagnose and efficiently treat diverse cancer types. © 2022 Elsevier Inc. All rights reserved.
Clinical Applications of Noncoding RNAs in Cancer
(Elsevier, 2022) Subash Chandra Gupta; Kishore B. Challagundla
Clinical Applications of Noncoding RNAs in Cancer summarizes the existing strategies, advances, and future opportunities on the role of noncoding RNAs in cancer patients. Established clinicians and researchers from all around the world share their views and expertise and provide readers with invaluable knowledge on the subject. This book provides a comprehensive collection of information on the utility of noncoding RNAs in the diagnosis, prognosis, and therapy of cancer. It also discusses the evolutionary significance of noncoding RNAs and how the molecular tools such as RNA-seq, RNA-FISH, ic-SHAPE, and quantitative real-time PCR help in the detection and elucidation of the functions of noncoding RNAs. Additionally, the challenges associated with noncoding RNA approaches and future developments are discussed. It is a valuable resource for cancer researchers, oncologists, clinicians, and other biomedical field members who want to learn more about noninvasive ways to diagnose and efficiently treat diverse cancer types. © 2022 Elsevier Inc. All rights reserved.
Clinico-pathological peculiarities of human papilloma virus driven head and neck squamous cell carcinoma: A comprehensive update
(Elsevier Inc., 2020) K. Devaraja; Sadhna Aggarwal; Sumit Singh Verma; Subash Chandra Gupta
Aims: The current article provides a detailed account of the current understanding of molecular and clinico-pathological aspects of Human papilloma virus (HPV) driven head and neck squamous cell carcinoma (HNSCC). Materials and methods: The literature review included most of the landmark trials and clinical studies related to the HPV driven HNSCC. Key findings: HPV positive HNSCC differ distinctly from HPV negative tobacco-related HNSCC, especially in oropharyngeal region. Therefore, the American joint committee on cancer`s latest manual for classification and staging of cancer suggests a separate staging system for HPV positive oropharyngeal cancers. Despite the younger patients being affected and the high propensity for cervical metastasis, the HPV positive oropharyngeal cancers respond much better to the treatment. The association with wild type TP53 and low EGFR expression confers the favorable prognosis in HPV driven HNSCC. Since the association is not universal, we suggest checking for p53 and EGFR expression status before considering de-intensification of therapy. In addition, the presence of matted lymph nodes and five or more nodes could mean relatively poorer prognosis, and are not suitable for de-intensification of therapy. The same is also true probably with higher T stage and co-existing tobacco use. The methods for the detection of p16, HPV DNA, HPV E6/E7 mRNA, anti-E6/E7 antibodies, in tissue, in serum and in saliva of patients, along with their clinical implications are also discussed. Significance: This article provides latest developments on the HPV driven HNSCC. ‘Diagnosis of transcriptionally active HPV infection,’ ‘Modalities for surveillance,’ ‘Implication of de-escalation of therapy’ are some of the critical issues that could serve the medical, the research as well as the patient communities. © 2020 Elsevier Inc.
Diagnostic, prognostic, and therapeutic significance of long non-coding RNA MALAT1 in cancer
(Elsevier B.V., 2021) Bela Goyal; Shashi Ranjan Mani Yadav; Nikee Awasthee; Sweety Gupta; Ajaikumar B. Kunnumakkara; Subash Chandra Gupta
Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) is a widely studied lncRNA in cancer. Although dispensable for normal physiology, MALAT1 is important for cancer-related pathways regulation. It is localized in the nuclear speckles periphery along with centrally located pre-RNA splicing factors. MALAT1 associated cancer signaling pathways include MAPK/ERK, PI3K/AKT, β-catenin/Wnt, Hippo, VEGF, YAP, etc. Molecular tools such as immunoprecipitation, RNA pull-down, reporter assay, Northern blotting, microarray, and q-RT-PCR has been used to elucidate MALAT1's function in cancer pathogenesis. MALAT1 can regulate multiple steps in the development of tumours. The diagnostic and prognostic significance of MALAT1 has been demonstrated in cancers of the breast, cervix, colorectum, gallbladder, lung, ovary, pancreas, prostate, glioma, hepatocellular carcinoma, and multiple myeloma. MALAT1 has also emerged as a novel therapeutic target for solid as well as hematological malignancies. In experimental models, siRNA and antisense oligonucleotide (ASO) based strategy has been used for targeting MALAT1. The lncRNA has also been targeted for the chemosensitization and radiosensitization of cancer cells. However, most studies have been performed in preclinical models. How the cross-talk of MALAT1 with other signaling pathways affect cancer pathogenesis is the focus of this article. The diagnostic, prognostic, and therapeutic significance of MALAT1 in multiple cancer types are discussed. © 2021 Elsevier B.V.
Drug repurposing for breast cancer therapy: Old weapon for new battle
(Academic Press, 2021) Sadhna Aggarwal; Sumit Singh Verma; Sumit Aggarwal; Subash Chandra Gupta
Despite tremendous resources being invested in prevention and treatment, breast cancer remains a leading cause of cancer deaths in women globally. The available treatment modalities are very costly and produces severe side effects. Drug repurposing that relate to new uses for old drugs has emerged as a novel approach for drug development. Repositioning of old, clinically approved, off patent non-cancer drugs with known targets, into newer indication is like using old weapons for new battle. The advances in genomics, proteomics and information computational biology has facilitated the process of drug repurposing. Repositioning approach not only fastens the process of drug development but also offers more effective, cheaper, safer drugs with lesser/known side effects. During the last decade, drugs such as alkylating agents, anthracyclins, antimetabolite, CDK4/6 inhibitor, aromatase inhibitor, mTOR inhibitor and mitotic inhibitors has been repositioned for breast cancer treatment. The repositioned drugs have been successfully used for the treatment of most aggressive triple negative breast cancer. The literature review suggest that serendipity plays a major role in the drug development. This article describes the comprehensive overview of the current scenario of drug repurposing for the breast cancer treatment. The strategies as well as several examples of repurposed drugs are provided. The challenges associated with drug repurposing are discussed. © 2019 Elsevier Ltd
Editorial: Targeting triple negative breast cancer by natural compounds
(Frontiers Media SA, 2023) Shashank Kumar; Sanjay Gupta; Subash Chandra Gupta
[No abstract available]
Efficacy of Cannabis and its Constituents in Disease Management: Insights from Clinical Studies
(Bentham Science Publishers, 2023) Divya Vimal; Leonard Clinton D’souza; Vipin Rai; Samridhi Lal; Anurag Sharma; Subash Chandra Gupta
There is a long history of informal use of Cannabis sativa (commonly called cannabis) for many purposes, including treating various ailments worldwide. However, the legalization of cannabis in multiple countries, specifically for medical purposes, has grabbed the researchers' attention to discover the scientific evidence regarding cannabis’s beneficial effects. Among over 500 identified compounds (cannabinoids), Δ9-Tetrahydro-cannabinol (THC) and cannabidiol (CBD) are two major active cannabinoids derived from cannabis. Cannabinoids exert their effects through cannabinoid receptors (CB1R and CB2R). In the recent past, clinical trials have shown the efficacy of cannabis and cannabinoids for various human ailments, such as cancer, neurological disorders, inflammatory bowel disease, chronic pain, and metabolic disorders. The commonly used constituents and derivatives of cannabis include CBD, THC, THCV, dronabinol, nabilone, and nabiximol. The cannabis constituents have also been used in combination with other agents, such as megestrol acetate, in some clinical trials. The common routes for the administration of cannabis are oral, sublingual, or topical. Cannabis has also been con-sumed through smoking, inhalation, or with food and tea. A maximum of 572 patients and a minimum of nine patients have participated in a single clinical trial. Cannabis is le-galized in some countries with restrictions, such as Belize, Canada, Colombia, Costa Ri-ca, The Czech Republic, Jamaica, Netherlands, South Africa, Spain, and Uruguay. This article provides a compilation of published studies focusing on clinal trials on the therapeutic effects of cannabis. The adverse effects of cannabis and its constituents are also discussed. © 2023 Bentham Science Publishers.
Evaluation of antioxidant, anti-inflammatory and anticancer activities of diosgenin enriched Paris polyphylla rhizome extract of Indian Himalayan landraces
(Elsevier Ireland Ltd, 2021) Debmalya Das Gupta; Shruti Mishra; Sumit Singh Verma; Anusmita Shekher; Vipin Rai; Nikee Awasthee; Tridip J. Das; Dipayan Paul; Sanjib K. Das; Hui Tag; Subash Chandra Gupta; Pallabi K. Hui
Ethnopharmacological relevance: Traditional medicinal plants have gained attention as a potential therapeutic agent to combat cancer and inflammation. Diosgenin rich fresh extracts of Paris polyphylla rhizome from Indian Himalaya is traditionally used as wound healing, anti-bleeding, anti-inflammatory and anti-cancer agent by the folk healers. Aim of the study: Present study was aimed to prepare two types of extracts from Paris polyphylla rhizome of Indian Himalayan landraces – 1. ethanolic extract of Paris polyphylla rhizome (EEPPR) and 2. Diosgenin enriched Paris polyphylla rhizome extract (DPPE), quantification of diosgenin content, and to evaluate their in vitro anti-oxidant, in vivo anti-inflammatory and in vitro cytotoxicity and anti-cancer activities of the DPPE. Materials and methods: Diosgenin content of EEPPR was quantified through GC-MS while diosgenin content of DPPE was quantified through HPTLC, and the diosgenin yield from EEPPR and DPPE were compared. In vitro antioxidant activities of DPPE were performed using DPPH, NOD, RP and SOD assay while in vivo anti-inflammatory activity of DPPE were evaluated in dextran induced hind paw edema in rats. In vitro cytotoxicity and anti-cancer activities of DPPE were evaluated in human breast cancer cell lines (MCF-7, MDA-MB-231), cervical cancer cell lines (HeLa) and Hep-2 cell lines. Results: EEPPR obtained through cold extraction method using 70% ethanol showed maximum diosgenin content of 17.90% quantified through GC-MS while similar compounds pennogenin (3.29%), 7β-Dehydrodiosgenin (1.90%), 7-Ketodiosgenin acetate (1.14%), and 7 β-hydroxydiosgenin (0.55%) were detected in low concentration, and thus confirmed diosgenin as major and lead phytochemical. However, DPPE obtained through both cold and repeated hot extraction with the same solvent (70% ethanol) showed diosgenin content of 60.29% which is significantly higher (p < 0.001) than the diosgenin content in EEPPR. DPPE demonstrated significant in vitro antioxidant activities by dose-dependently quenched (p < 0.001) SOD free radicals by 76.66%, followed by DPPH (71.43%), NOD (67.35%), and RP (63.74%) at a max concentration of 2 μg/μl of ascorbic acid and test drugs with remarkable IC50 values (p < 0.01). Further, DPPE also showed potent anti-inflammatory activities by dose-dependently suppressed dextran induced paw edema in rats (p < 0.01) from 2 h to 4 h. DPPE suppressed the proliferation of MCF-7, MDA-MB-231, Hep-2 and HeLa cell lines. Maximum activity was observed in MCF-7 cells. The DPPE also induced apoptosis in MCF-7 cell lines as measured by AO/PI and DAPI staining, as well as DNA laddering, cell cycle analysis and phosphatidylserine externalization assay. The growth-inhibitory effect of DPPE on MCF-7 breast cancer cells was further confirmed from the colony-formation assay. DPPE upregulated expression of Bax and downregulated Bcl-2 and survivin mRNA transcripts. Conclusion: DPPE obtained through both cold and repeated hot extraction using ethanol showed significantly higher content of diosgenin than the diosgenin content detected in EEPPR. However, diosgenin yield of both the extracts (EEPPR & DPPE) clearly confirmed diosgenin as major and lead phytochemical of Paris polyphylla rhizome of Indian Himalayan landraces. Further, DPPE also demonstrated potent in vitro anti-oxidative and in vivo anti-inflammatory activities and showed in vitro cytotoxicity and significant anti-cancer (apoptosis) effects in MCF-7 breast cancer cells. © 2021
Evaluation of Efficacy of Curcumin and Caffeic Acid Phenethyl Ester in Breast Cancer by Preclinical Studies
(Bentham Science Publishers, 2025) Sumit Singh Verma; Avadhesh; Ankit Srivastava; Anusmita Shekher; Anupam Dhasmana; Acharan Singh Narula; Subash Chandra Gupta
Aims: The aim of this study was to evaluate the combined and comparative efficacy of Caffeic acid phenethyl ester (CAPE) and curcumin in breast cancer. Background: CAPE and curcumin are a class of phenolics. While curcumin is obtained from turmeric, CAPE is found in Baccharis sarothroides and Populus deltoides. Both agents are reported to produce activities in some cancer types. The combined and comparative effects of the two agents in breast cancer have not yet reported. Objective: We evaluated the potential of CAPE and curcumin in both in vitro and in vivo breast cancer models. Methods: Human breast cancer cell lines, MDA-MB-231 and MCF-7, were exposed to CAPE and curcumin, followed by functional assays such as cell cytotoxicity, cell proliferation and colony formation, cell cycle, mitochondrial membrane potential, apoptosis, and monodansylcadaverine (MDC) staining for autophagy. Computational analyses and mouse models were also used. Results: Employing computational analyses, both agents were found to exhibit drug-like properties. Both molecules interacted with the key molecules of the NF-κB pathway. CAPE and curcumin inhibited cell proliferation, colony formation, and invasion, triggering apoptosis in breast cancer cells. CAPE was found to be more effective than curcumin. Two agents working together were more effective than each agent working alone. Both agents suppressed the expression of survivin, Bcl-xL and GLUT-1. The level of cleaved PARP was increased by both agents. Both phenolics observed an induction in ROS generation. Further, both molecules triggered a dissipation in mitochondrial membrane potential. In mice models implanted with Ehrlich-Lettre ascites carcinoma (EAC) cells, both drugs inhibited the growth of the tumour. The phenolics also modulated the metabolic parameters in tumour-bearing mice. Conclusion: The observations suggest that the combination of curcumin plus CAPE may be better in comparison to individual molecules. Other: The study opens a window for analysing the efficacy of the combination of CAPE and curcumin in animal studies. This will provide a basis for examining the combined efficacy of two agents in a clinical trial. © 2025 Bentham Science Publishers.
Evaluation of lignin and cellulose nanoparticles from bacterial-deconstructed sugarcane bagasse for effective quercetin delivery
(Elsevier B.V., 2025) Gaurav Singh; Abhishek Verma; Ankit Srivastava; Subash Chandra Gupta; Tamal Mandal; Dalia Dasgupta Mandal
This study attempts an innovative biorefinery strategy to valorize sugarcane bagasse (SCB), producing nanomaterials for targeted drug delivery for the hydrophobic drug Quercetin. Bacterial strain Ectopseudomonas mendocina NITDDGIFE11 was employed to delignify Sugarcane bagasse (SCB) via batch-submerged fermentation, and analyzed for alteration in its structural and chemical content. The extracted biopolymers lignin and cellulose, characterized via FESEM, XRD, and FTIR, were transformed into their respective lignin (LNPI) and cellulose (CNPI) nanoparticles, found to have size averaging 279.4 and 207.25 nm via DLS and validated by HRTEM (<150 nm), XRD, FTIR, and FT-RAMAN. Both these nanoparticles were found to act as good delivery vehicles for Quercetin, where LNPI-Q demonstrated superior encapsulation (84.413 %) and loading capacity (36.30 %) relative to CNPI-Q and enhanced antioxidant activity compared to their free form. They exhibited sustained Quercetin release over 6 days and followed first-order kinetics. Reduced toxicity in HEK-293 cells revealed the host compatibility of the free LNP and CNP as a delivery system, while Quercetin-loaded forms exhibited significant anticancer activity, as examined in the triple-negative breast cancer cell line MDA-MB-231. Biocompatibility was further validated through haemolytic and phytotoxicity assays, confirming safety. Apart from biopolymer valorisation, a few interesting low molecular weight aromatic compounds (LMWACs) were also noticed in the bacterial-treated liquid fraction of SCB using LC-MS study. The outcome of this study not only provides a development of a drug delivery system from lignocellulosic biomass, but also may help in agricultural waste management and circular bioeconomy. © 2025 Elsevier B.V.
Genes involved in phosphatidylcholine biosynthesis correlate with nuclear factor-κB in biliary tract cancer patients: Evidence from 1H NMR and computational analyses
(Elsevier B.V., 2021) Anusmita Shekher; Amit Kumar Tiwari; Nikee Awasthee; Sumit Singh Verma; Vinod Kumar Dixit; Neeraj Sinha; Subash Chandra Gupta; Puneet
Gallbladder cancer (GBC) is an aggressive malignancy of gastrointestinal tract. Due to uncontrolled growth, GBC cells rapidly synthesize biomolecules including lipids. The lipids are integral component of cell membrane with a wide range of cellular functions. In this study, we measured the clinicopathological features in 40 cases of histologically confirmed GBC and 16 cases of chronic cholecystitis (CC). The female to male ratio in the GBC and CC groups were 3.44:1 and 2.2:1, respectively. The GBC patients exhibited well to poorly differentiated tumor. In the CC group, all patients showed cholecystitis with no evidence of dysplasia or malignancy. The majority of GBC and CC patients reported pain. Using 1H NMR spectroscopy, we observed 4-folds increase in the level of choline containing phospholipids (CCPLs) in the gallbladder of GBC patients as compared to CC patients. Other lipid metabolites such as cholesterol ester, C18-cholesterol and saturated fatty acids were insignificantly changed between GBC and CC patients. Moreover, the level of CCPLs in the GBC patients with BMI <25 kg/m2 was significantly higher as compared to CC patients. Further, a significant increase in the CCPLs level was observed in GBC female patients in comparison to CC patients. From the computational analyses, we observed that the genes involved in the biosynthesis of phosphatidylcholine (PtdCho) indirectly interact with the RELA, which encodes the NF-κB p65 subunit. The genes involved in the PtdCho biosynthesis were also correlated with the overall and disease-free survival of cholangiocarcinoma patients. The study opens new window for exploring the diagnostic and therapeutic potential of CCPLs in GBC patients. © 2021 Elsevier B.V.