Browsing by Author "Manickam, Paulpandi"

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THE CREATION OF SELENIUM NANOPARTICLES DECORATED WITH TROXERUTIN AND THEIR ABILITY TO ADAPT TO THE TUMOUR MICROENVIRONMENT HAVE THERAPEUTIC IMPLICATIONS FOR TRIPLE-NEGATIVE BREAST CANCER
(The Royal Society of Chemistry, 2023) Thiruvenkataswamy, Saranya; Krishnamoorthy, Kavithaa; Manickam, Paulpandi; Sennimalai, Ramya; Sureshbabu, Harysh Winster; Geetha, Mani; Sangeetha, Dhayalan; Vellingiri, Balachandar; Arul, Narayanasamy
Despite advancements in treatment, managing aggressive types of breast cancer, particularly Triple Negative Breast Cancer (TNBC), remains a daunting task. Newer chemotherapeutics enhance the multidrug resistance in cancer cells, making them untreatable. The current research work was framed to develop a novel therapeutic target by utilizing the flavanol, troxerutin (TXN) as a drug of interest to target TNBC. And also, to increase the efficiency of the drug at the target site, a nanocarrier called selenium nanoparticles (SeNPs) has been exploited. Thus, the anticancer efficacy of TXN and Se–TXN against TNBC (in vitro and in vivo) has been compared and analysed in the present study. Se–TXN was synthesized by a precipitation approach and characterized by diverse analytical techniques, which confirmed the successful loading of TXN on the SeNPs. The inhibitory concentration (IC50) of Se–TXN was determined to be 6.5 ± 0.5 μg mL−1 according to the in vitro data. Even at lower concentrations, the existence of apoptotic bodies shows that Se–TXN is effective against TNBC. Additionally, the Se–TXN expression study shows that the activation of the caspase cascade pathway, which results in apoptosis, occurs from the downregulation of anti-apoptotic proteins and genes and the upregulation of pro-apoptotic proteins and genes. And the in vivo investigations like histopathology, hematology and biochemical parameters revealed that the Se–TXN had significantly lowered the tumour volume of treated Balb/C mice without having any significant systemic toxicity when compared to other treatment groups. Altogether, our data suggests the efficacy of Se–TXN nanoconjugates as an effective management therapy for treating TNBC.
THE CREATION OF SELENIUM NANOPARTICLES DECORATED WITH TROXERUTIN AND THEIR ABILITY TO ADAPT TO THE TUMOUR MICROENVIRONMENT HAVE THERAPEUTIC IMPLICATIONS FOR TRIPLE-NEGATIVE BREAST CANCER
(Royal Society of Chemistry, 2023-02-09) Thiruvenkataswamy, Saranya; Krishnamoorthy, Kavithaa; Manickam, Paulpandi; Sennimalai, Ramya; Sureshbabu Harysh, Winster; Geetha, Mani; Sangeetha, Dhayalan; Vellingiri, Balachandar; Arul, Narayanasamy
Despite advancements in treatment, managing aggressive types of breast cancer, particularly Triple Negative Breast Cancer (TNBC), remains a daunting task. Newer chemotherapeutics enhance the multidrug resistance in cancer cells, making them untreatable. The current research work was framed to develop a novel therapeutic target by utilizing the flavanol, troxerutin (TXN) as a drug of interest to target TNBC. And also, to increase the efficiency of the drug at the target site, a nanocarrier called selenium nanoparticles (SeNPs) has been exploited. Thus, the anticancer efficacy of TXN and Se–TXN against TNBC (in vitro and in vivo) has been compared and analysed in the present study. Se–TXN was synthesized by a precipitation approach and characterized by diverse analytical techniques, which confirmed the successful loading of TXN on the SeNPs. The inhibitory concentration (IC50) of Se–TXN was determined to be 6.5 ± 0.5 μg mL−1 according to the in vitro data. Even at lower concentrations, the existence of apoptotic bodies shows that Se–TXN is effective against TNBC. Additionally, the Se–TXN expression study shows that the activation of the caspase cascade pathway, which results in apoptosis, occurs from the downregulation of anti-apoptotic proteins and genes and the upregulation of pro-apoptotic proteins and genes. And the in vivo investigations like histopathology, hematology and biochemical parameters revealed that the Se–TXN had significantly lowered the tumour volume of treated Balb/C mice without having any significant systemic toxicity when compared to other treatment groups. Altogether, our data suggests the efficacy of Se–TXN nanoconjugates as an effective management therapy for treating TNBC
ENHANCED APOPTOGENESIS AND ONCOGENE REGULATORY MECHANISM OF TROXERUTIN IN TRIPLE NEGATIVE BREAST CANCER CELLS
(Oxford University Press, 2020) Thiruvenkataswamy, Saranya; Krishnamoorthy, Kavithaa; Manickam, Paulpandi; Sennimalai, Ramya; Sivashanmugam, Preethi; Vellingiri, Balachandar; Arul, Narayanasamy
Triple negative breast carcinoma (TNBC) is an aggressive form of cancer, with high rates of morbidity, mortality, poor prognosis and limited therapeutic options. The objective of the present study was to elaborate the anticancer activity of Troxerutin (TXN) in TNBC/MDA-MB-231 cells. Herein, we demonstrated the inhibitory effects of TXN on the breast cancer cell growth via induction of apoptosis. Mitochondrial membrane potential (m), DNA damage and apoptotic nuclear changes were analyzed by f lowcytometry, AO/EtBr and Hoechst staining, respectively. Furthermore, apoptotic protein and gene expressions were analyzed by western blot and reverse transcription polymerase chain reaction (RT-PCR), respectively. Our results indicated that TXN induces apoptosis as evidenced by inhibit the cell proliferation, enhanced apoptotic activation, altered mitochondrial membrane potential and elevated level of DNA damage in TNBC cells. Furthermore, the TXN inhibit anti-apoptotic protein expression with the subsequent upregulation of Cytochrome c, Caspase-9 and Caspase-3. Thus, TXN induces apoptosis in TNBC cells through inducing nuclear damage and altered apoptotic marker expressions. Therefore, TXN might be used as a potential therapeutic agent for the treatment of triple negative breast cancer
FABATIN-LOADED SILICA NANOPARTICLE-INDUCED APOPTOSIS VIA MITOCHONDRIAL DYSFUNCTION: TARGETING THE PI3K/AKT MOLECULAR PATHWAY AS A THERAPEUTIC IMPLICATION AGAINST TRIPLE NEGATIVE BREAST CANCER
(The Royal Society of Chemistry, 2021) Sennimalai, Ramya; Manickam, Paulpandi; Krishnamoorthy, Kavithaa; Thiruvenkataswamy, Saranya; Harysh, Winster; Vellingiri, Balachandar; Arul, Narayanasamy
Although chemotherapeutics plays a pivotal role in the therapy of many aggressive cancers, there are many pitfalls including multidrug resistance and lack of selectivity which result in progression of the cancer. Triple negative breast cancer (TNBC) is one such aggressive type of breast cancer with minimal therapeutic approaches. As TNBC is associated with high risk of metastasis and low survival percentage, an immense requisite to expand the therapeutic strategy is needed. In support of this quest, an attempt was made to exploit the anticancer efficacy of fabatin, a phytodefensin peptide obtained from the seeds of Vicia faba, along with the biocompatible nanocarrier silica as a therapeutic strategy against TNBC. The current work was intended to isolate the plant defensin cationic antimicrobial peptide fabatin from the seeds of Vicia faba and also to load it in mesoporous silica nanoparticles (F-SNP) to increase its efficiency in the TNBC system, both in vitro using MDA-MB-231 cells and in vivo in a xenograft mice model. In vitro studies demonstrated the efficient role of F-SNP against MDA-MB-231 cells with inhibitory concentration (IC50) of 7.8 ± 0.9 μg mL−1 while showing least significant effect on normal breast MCF-10A cells. The appearance of apoptotic bodies specifies the cell death promoted by isolated cationic defensin peptide fabatin. Moreover, expression studies evinced the downregulation of PI3K which further resulted in the upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins. Further in vivo studies supported our in vitro findings by confirming a significant reduction in tumor volume. Histopathological observations confirm the absence of noteworthy effect in F-SNP treated mice model. Our findings altogether indicated F-SNP to be a most promising drug with significant pharmaceutical potential in the treatment of TNBC cells.
GREEN SYNTHESIS OF SELENIUM NANOPARTICLES USING SOLANUM NIGRUM FRUIT EXTRACT AND ITS ANTI-CANCER EFFICACY AGAINST TRIPLE NEGATIVE BREAST CANCER
(SpringerLink, 2022-08-15) Thiruvenkataswamy, Saranya; Sennimalai, Ramya; Krishnamoorthy, Kavithaa; Manickam, Paulpandi; Yong-Pil, Cheon; Sureshbabu, Harysh Winster; Vellingiri, Balachandar; Arul, Narayanasamy
The contemporary study aims at the synthesis of selenium nanoparticles (SeNPs) through green synthesis by utilizing fruit extract of Solanum nigrum and to evaluate its anti-oxidant, anti-bacterial, and anti-cancer activity. Then the synthesized SeNPs had been characterized with UV–Vis spectroscopy, FTIR, XRD, Dynamic Light Scattering, Zeta potential and scanning electron microscopy. The results had shown the successful synthesis of SeNPs which was found to be spherical in shape and has a particle diameter of 87 nm. Further, the FTIR spectrum confirms the presence of various functional groups of the plant extract, which could probably influence the reduction and stabilization of SeNPs. Also the synthesized SeNPs had exhibited a significant dose dependent reduction of free radicals as depicted by DPPH assay. Further the SeNPs had inhibited the proliferation of selected gram-positive and gram- negative bacteria in a dose dependent way indicating their significant anti-bacterial property. Then, the anti-cancer efficacy of the SeNPs against the triple negative breast cancer was analysed by MTT and was found to exhibit an IC50 of 19 µg/ml. These results collectively displays the bioactive potential including anti-oxidant, anti-bacterial, and anti-cancer efficacy posed by the SeNPs which could possibly be explored further for their efficient therapeutics in near future.
NOVEL THERAPEUTIC APPROACHES TARGETING CANCER STEM CELLS: UNVEILING NEW FRONTIERS IN BREAST CANCER TREATMENT (Review)
(Elsevier, 2025-02-01) T C, Deeptha; N K, Nabeela; Pushparaj, Charumathi; Narayanasamy, Arul; Manickam, Paulpandi; Thiruvenkataswamy, Saranya; Sennimalai, Ramya
Breast cancer remains the leading cause of mortality among women with cancer. This article delves into the intricate relationship between breast cancer and cancer stem cells (CSCs), emphasizing advanced methods for their identification and isolation. The key isolation techniques, such as the mammosphere formation assay, surface marker identification, Side Population assay, and Aldehyde Dehydrogenase assay, are critically examined. Furthermore, the review analyzes CSC-specific molecular signaling pathways, focusing on actionable targets like CD44/CD24, Nanog, and Oct4. The potential of targeted therapies and small molecules that disrupt these pathways is explored. Additionally, the review highlights immunotherapy strategies against CSCs, focusing on resistance mechanisms and the critical role of precision medicine. The study investigates how precision medicine enhances therapeutic outcomes by targeting specific CSC biomarkers. This comprehensive analysis offers insights into recent advancements and emerging strategies in breast cancer treatment, pointing toward future therapeutic innovations.
PH DEPENDENT DRUG RELEASE OF SILIBININ, A POLYPHENOL CONJUGATED WITH MAGNETIC NANOPARTICLE AGAINST THE HUMAN COLON CANCER CELL
(SpringerLink, 2020-04-03) Sennimalai, Ramya; Saranya, Thiruvenkataswamy; Krishnamoorthy, Kavithaa; Sivashanmugam, Preethi; Harysh, Winster; Vellingiri, Balachander; Manickam, Paulpandi; Arul, Narayanasamy
Magnetic nanocarriers has become popularised in the research field as well as in the biomedical application due to their unique exotic possession, and processability. The present study involves the synthesis of nanocarrier, Iron Oxide nanoparticle conjugated with silibinin (SLN-Fe2O3) using co-precipitation method and also to detect their efficacy against the colon cancer cell. The synthesized SLN-Fe2O3 were undertaken for several analysis including UV-visible spectroscopy, dynamic light scattering, scanning electron microscope, Fourier transform infra-red spectroscopy, zeta potential analysis, and X-ray diffraction analysis. The analysis had end up in confirming the polydispersity and crystalline nature of the synthesized SLN-Fe2O3 with an average size of 70 nm. Further the synthesized SLN-Fe2O3 was undertaken for in vitro (AO/EtBR and DAPI) studies to find their effectiveness against human colon cancer using HT-29 cell line. The fragmentation occurs in nuclear material of the SLN-Fe2O3 treated cells had revealed that the cell death was due to the induction of apoptotic signals in the treated cancer cells. Thus the current study had clearly validated the potency of synthesized Iron Oxide nanoparticles conjugated with silibinin (SLN-Fe2O3) against the colon cancer cell and holds a promising therapeutic potency in treating cancer cells.
REDUCED GRAPHENE OXIDE NANOPLATELETS DERIVED FROM THE ZIZIPHUS MAURITIANA: BIO-MEDIATED SYNTHESIS AND ANTIMICROBIAL AND ANTICANCER ACTIVITIES
(Elsevier, 2024-02) Thirumoorthy, Poongodi; Manickam, Paulpandi; Krishnamoorthy, Kavithaa; Giriraj, Kalaiarasi; Rajapandian, Rajaganesh; Sangeetha, Dhayalan; Veerapandiyan, Ramabhai; Chandran, Sharmila
A unique technique was used to synthesize reduced graphene oxide (rGO) from graphene oxide (GOX) using Ziziphus mauritiana plant leaf extract as both a reducing agent as well stabilizing agent. We examined the green, efficient, and cost-effective method for producing reduced graphene oxide nanoparticles by utilizing selected plant. This study utilized a range of analytical techniques, such as Ultraviolet Visible Spectroscopy (UV–Vis), Fourier transform infrared Spectroscopy (FTIR), X-Ray diffraction analysis (XRD), Zeta potential measurement, and Scanning Electron Microscope (SEM) in order to confirm the successful green production of reduced graphene oxide nanoplatlets. Our work reveals that reduced graphene oxide generally exhibits a layered structure characterized by smooth surfaces, transparency, and wavy patterns. The antibacterial activity was determined by analyzing the values of minimal inhibitory concentration (MIC) with agar diffusion method. The synthesized graphene material showed more effectiveness against E.coli and S.aureus. The increased concentration correspondingly led to an increase in bacterial growth inhibition. The highest zone of inhibition (ZOI) observed was 9 mm for E.coli and 10 mm for S. aureus at a concentration of 100 μg/ml. The efficacy of reduced graphene oxide (rGO) in combating cancer was evaluated using MCF-7 human breast cancer cells. The IC50 of the synthesized rGO against the chosen cancer cells was found to be 12.3 ± 0.8 μg/ml, which is comparable to the standard drug. The results suggest that rGO has significant potential as an anticancer agent for selected human bacterial pathogen as well human cancer cells.
SITOSTEROL-FABRICATED CHITOSAN NANOCOMPLEX INDUCES APOPTOTIC CELL DEATH THROUGH MITOCHONDRIAL DYSFUNCTION IN LUNG CANCER ANIMAL MODEL: AN ENHANCED SYNERGETIC DRUG DELIVERY SYSTEM FOR LUNG CANCER THERAPY
(The Royal Society of Chemistry, 2021) Krishnamoorthy, Kavithaa; Manickam, Paulpandi; Sennimalai, Ramya; Mathan, Ramesh; Vellingiri, Balachandar; Karthikeyan, Ramasamy; Arul, Narayanasamy
Lung carcinoma is an aggressive form of cancer, with an increasing rate of morbidity, dismal outlook, poor prognosis and limited therapeutic approaches. The present study is aimed to demonstrate the anticancer efficacy of a fabricated beta-sitosterol chitosan nanocomplex (BSC) in a human lung cancer cell line (A-549) and animal model. The nanocomplex was fabricated using beta-sitosterol and chitosan and its properties were investigated via FTIR, DLS, zeta potential, SEM, and TEM. In vitro and in vivo assessments were done employing various techniques to determine the viability and alterations in morphology of A-549 cells, and also the anti-tumor efficacy in a xenograft mice model. The outcomes revealed the apoptotic efficacy prompted by the BSC nanocomplex in both a time- and dose-dependent manner. Subsequently, AO/EB staining of the BSC nanocomplex at different concentrations led to the typical alteration in the morphology of the cells, comprising the shrinkage of cells and fragmented nucleus, resulting in apoptosis. The effect of the BSC nanocomplex on the cell cycle phase distribution and mitochondrial membrane potential was evaluated using flow cytometry. There was a notable loss in the mitochondrial membrane potential, which ultimately caused an apoptotic effect in the treated cells. Also, the BSC nanocomplex reduced the migratory potential of the A-549 cells in vitro. Moreover, the in vivo studies corroborated our in vitro findings and emphasized the decrease in tumor volume of the established xenograft mice model. The histopathological study also confirmed the absence of any noteworthy effects caused by the BSC nanocomplex in the major organs of the treated mice. Thus, the present findings clearly demonstrate that the BSC nanocomplex paves a way as a new agent to be used for therapeutic targeting in cancer treatment.
SPATHULENOL ATTENUATES 6-HYDROXYDOPAMINE INDUCED NEUROTOXICITY IN SH-SY5Y NEUROBLASTOMA CELLS
(Elsevier, 2021-12) Ragesh, Babu Manjima; Sennimalai, Ramya; Krishnamoorthy, Kavithaa; Manickam, Paulpandi; Thiruvenkataswamy, Saranya; Suresh Babu, Harysh Winster; Vellingiri, Balachandar; Narayanasamy, Arul
Neurodegeneration is a progressive loss of neuronal function in certain parts of brain and spinal cord which lead to many neurodegenerative disorders. Phytocompounds has become a reliable treatment for numerous diseases as they uphold various biological properties within them. The present study had explored the neuroprotective efficacy of spathulenol (component of essential oil) in vitro in SH-SY5Y neuroblastoma cells by inducing neuronal damage through treatment with 6-hydroxydopamine (6-OHDA). To demonstrate the efficacy of spathulenol various assays involving testing its potency on reducing the ROS production, maintaining the mitochondrial integrity, and also its role in neuroprotection was validated through SH-SY5Y cells. The cells were treated with 6-OHDA (100 μM) and spathulenol (1 to 20 μM). Our results depicted that the cells treated with 6-OHDA alone causes membrane blebbing and cell shrinkage while the treatment with both 6-OHDA and spathulenol had ensued recovery of damaged cells in dose dependent way. The study had also highlighted the neuroprotective property of spathulenol amidst 6-OHDA treatment through relieving the cells from oxidative stress and also by maintaining the mitochondrial membrane integrity. These results had evinced the use of spathulenol in restoring the abnormal cellular conditions induced by 6-OHDA in neuronal cells highlighting it as a potential promising therapy for treating neurodegenerative diseases.
SYNTHESIS, CHARACTERIZATION OF C-ZN/PD-NP AS POTENTIAL NANOCOMPOSITES AGAINST HUMAN LUNG CANCER CELLS (A549) AND PATHOGENIC MICROORGANISMS
(Springer, 2024-06-15) dhorai, Niveditha; Manickam, Paulpandi; Rangaraj, Suriyaprabha; Venkatachalam, Rajendran
Palladium wrapped ZnO nanocomposites synthesis through carrageenan were made as bimetallic nanocomposites (C-Zn/Pd-Np) and their antibacterial and anticancer efficacy were assessed under in vitro condition. Further, they were physico-chemically characterized. The metal complex was subjected to characterization by a range of physico-chemical techniques, encompassing scanning electron microscopy (SEM), X-ray diffraction (XRD), and infrared spectroscopy (FT-IR). According to the X-ray diffraction (XRD) study, the bimetallic nanocomposites exhibit a higher degree of crystallinity. The antibacterial activity of the nanocomposites was assessed using Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Escherichia coli as test organisms. The outcomes demonstrated significant antibacterial efficacy against all of the investigated pathogens. The antiproliferative effectiveness of the nanocomposites against A549 cancer cell types are significantly enhanced with an increased concentration. It also resulted in cell cycle arrest, apoptosis, and necrosis found in bimetallic nanocomposites treated cells. In conclusion, (C-Zn/Pd-Np) has notable antibacterial action and is effective against at inhibiting the growth of lung cancer cells. According to this present study, C-Zn/Pd-Np may be useful for the effective clinical management of Human pathogens and lung cancer cells.