Browsing by Author "Arul, Narayanasamy"

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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.
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.
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.