Browsing by Author "Chowdhury, Rajdeep"

Now showing 1 - 20 of 80

Aggregation induced emission’ active iridium(iii) complexes with applications in mitochondrial staining
(RSC, 2017) Chowdhury, Rajdeep; Laskar, Inamur Rahaman
Two new bis-cyclometalated iridium(III) complexes, [Ir(F2ppy)2(L)] and [Ir(ppy)2(L)], where F2ppy = 2-(2′,4′-difluoro)phenylpyridine, ppy = 2-phenylpyridine and L = 1,2-((pyridin-2-ylimino)methyl)phenol, have been designed and synthesized by a convenient route. We have univocally characterized their structure by 1H NMR, 19F NMR, HRMS and SXRD. Both complexes exhibit strong ‘Aggregation Induced Emission (AIE)’ activity, which has been investigated using spectroscopy measurements, ab initio quantum chemical calculations and by analysing their crystal packing. One of the complexes has been shown to have a potential application as a non-toxic bio-imaging probe for mitochondrial staining.
Arsenic extrusion and energy derivation as survival mechanism in a novel exiguobacterium isolated from arsenic contaminated groundwater of West Bengal
(IASIR, 2014) Chowdhury, Rajdeep
The Bengal-Delta plain at Indo-Bangladesh border is severely affected with groundwater arsenic contamination. The microbial diversity of this site is totally uncharacterized. Here we report the existence of a novel Exiguobacterium strain that could thrive under high arsenic concentrations in the arsenic-infested water of the above region. Drinking water was sampled for presence of bacterial isolates. Analysis of the 16SrRNA sequence of the bacteria isolated revealed them to be members representing various genera. Of particular interest was a new species of genera Exiguobacterium (=MTCC 7757T=JCM 13946T) that thrived in extremely high arsenic concentration, arsenate (30mM) and arsenite (20mM). The growth-rate of the bacterium cultured in arsenate-supplemented medium increased significantly; it gained metabolic energy from arsenate-amended aerobic growth conditions. On analysis of the ars-operon, the strain was positive for arsB, but the genetic contribution to arsenate reduction (arsC) was not recognized, though a differential arsenate reductase activity could be observed. An increased expression of arsB, as an associated process to arsenate reduction, confirmed that arsenic extrusion principle worked behind its survival. Identification of such a bacterium could add to the diversity of bacteria specific to that geographical location and also help us in delineating putative novel arsenic resistance mechanisms operative for survival
Arsenic induced apoptosis in malignant melanoma cells is enhanced by menadione through ROS generation, p38 signaling and p53 activation
(Springer, 2008) Chowdhury, Rajdeep
Resistance to apoptosis is a prominent feature of melanoma. Pharmacological concentration of arsenic in combination with a widely known oxidant, menadione was explored in this study to synergistically sensitize malignant melanoma cells to apoptosis. The molecular mechanism of apoptosis and the signalingpathways involved were thoroughly investigated. Materials methods and results Menadione synergized NaAsO2 to significantly increase ROS generation and facilitate the major apoptotic signaling events: alteration of mitochondrial membrane potential, cytochrome c release and anti-apoptotic protein Bcl-2 down-regulation and subsequent activation of caspase-9 and caspase-3 followed by poly-ADP-ribose polymerase-1 cleavage. Antioxidant N-acetyl-L-cysteine antagonized these events. Investigation of the signaling-pathway revealed significant suppression of AP-1 activity but not NF-jB upon NaAsO2 and menadione application. An increase in p38 phosphorylation and p53 protein expression did also dictate the apoptotic response. Suppression of p38 activation with SB203580 and inhibition of p53 expression by siRNA attenuated apoptosis.
Arsenic Toxicity: Remediation and Treatment
(Taylor & Francis, 2016) Chowdhury, Rajdeep; Verma, S.K.; Mukherjee, Sudeshna
Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression
(PMC, 2010) Chowdhury, Rajdeep
Arsenic is a well-established human carcinogen; however molecular mechanisms to arsenic-induced carcinogenesis are complex and elusive. The present study identifies a potential biomarker of arsenic exposure, and redefines arsenic-induced signaling in stimulation of cell proliferation. The effect of arsenic exposure on gene expression was evaluated in PBMC of arsenic-exposed individuals selected from a severely affected district of West Bengal, India. A novel, un-documented biomarker of arsenic exposure, CyclinA was identified by microarray analysis from the study. Non-transformed cell lines HaCat and Int407 when exposed to clinically achievable arsenic concentration showed significant increase of CyclinA substantiating the clinical data. An associated increase in S phase population of cells in cell cycle, indicative of enhanced proliferation was also noticed. On further investigation of the pathway to arsenic-induced proliferation, we observed that arsenic resulted: ROS generation; activated Erk signaling; stimulated AP-1 activity, including immediate early genes, c-Jun and c-Fos. N-Acetyl-l-cysteine, a ROS quencher, blocked the arsenic-induced effects. Our study underlines a previously undefined mechanism by which arsenic imparts its toxicity and results in uncontrolled cell proliferation.
Autophagy inhibition potentiates SAHA‑mediated apoptosis in glioblastoma cells by accumulation of damaged mitochondria
(Spandidos, 2018) Chowdhury, Rajdeep; Roy, Aniruddha; Mukherjee, Sudeshna
Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ. The potential to evade apoptosis by GBM cells accentuates the need to target the non‑apoptotic pathway and/or inhibition of pro‑survival strategies that contribute to its high resistance to conventional therapies. In recent studies, it has been demonstrated that HDAC inhibitors, such as vorinostat (suberoyl anilide hydroxamic acid; SAHA) can induce autophagy in cancer cells, thereby stimulating autophagosome formation. In addition, a lysosomotropic agent such as chloroquine (CQ) can result in hyper‑accumulation of autophagic vacuoles by inhibiting autophagosome‑lysosome fusion, which can drive the cell towards apoptosis. Hence, we postulated that combination treatment with SAHA and CQ may lead to increased formation of autophagosomes, resulting in its hyper‑accumulation and ultimately inducing cell death in GBM cells. In the present study, we demonstrated that CQ co‑treatment enhanced SAHA‑mediated GBM cell apoptosis. Inhibition of the early stage of autophagy by 3‑methyladenine pre‑treatment reduced cell death confirming that apoptosis induced by CQ and SAHA was dependent on autophagosome accumulation. We also demonstrated that autophagy inhibition led to enhanced ROS, mitochondria accumulation and reduced mitochondrial membrane potential resulting in cell death. The present study provides cellular and molecular evidence concerning the combined effect of SAHA and CQ which can be developed as a therapeutic strategy for the treatment of glioblastoma in the future.
Autophagy inhibition potentiates SAHA‑mediated apoptosis in glioblastoma cells by accumulation of damaged mitochondria
(Spandidos Publications, 2018-04) Chowdhury, Rajdeep; Roy, Aniruddha
Glioblastoma multiforme (GBM), often referred to as a grade IV astrocytoma, is the most invasive type of tumor arising from glial cells. The main treatment options for GBM include surgery, radiation and chemotherapy. However, these treatments tend to be only palliative rather than curative. Poor prognosis of GBM is due to its marked resistance to standard therapy. Currently, temozolomide (TMZ), an alkylating agent is used for treatment of GBM. However, GBM cells can repair TMZ‑induced DNA damage and therefore diminish the therapeutic efficacy of TMZ. The potential to evade apoptosis by GBM cells accentuates the need to target the non‑apoptotic pathway and/or inhibition of pro‑survival strategies that contribute to its high resistance to conventional therapies. In recent studies, it has been demonstrated that HDAC inhibitors, such as vorinostat (suberoyl anilide hydroxamic acid; SAHA) can induce autophagy in cancer cells, thereby stimulating autophagosome formation. In addition, a lysosomotropic agent such as chloroquine (CQ) can result in hyper‑accumulation of autophagic vacuoles by inhibiting autophagosome‑lysosome fusion, which can drive the cell towards apoptosis. Hence, we postulated that combination treatment with SAHA and CQ may lead to increased formation of autophagosomes, resulting in its hyper‑accumulation and ultimately inducing cell death in GBM cells. In the present study, we demonstrated that CQ co‑treatment enhanced SAHA‑mediated GBM cell apoptosis. Inhibition of the early stage of autophagy by 3‑methyladenine pre‑treatment reduced cell death confirming that apoptosis induced by CQ and SAHA was dependent on autophagosome accumulation. We also demonstrated that autophagy inhibition led to enhanced ROS, mitochondria accumulation and reduced mitochondrial membrane potential resulting in cell death. The present study provides cellular and molecular evidence concerning the combined effect of SAHA and CQ which can be developed as a therapeutic strategy for the treatment of glioblastoma in the future.
Autophagy Regulated by Gain of Function Mutant p53 Enhances Proteasomal Inhibitor-Mediated Cell Death through Induction of ROS and ERK in Lung Cancer Cells
(Hindawi, 2019) Chowdhury, Shibasish; Chowdhury, Rajdeep; Mukherjee, Sudeshna
Mutations in p53, especially gain of function (GOF) mutations, are highly frequent in lung cancers and are known to facilitate tumor aggressiveness. Yet, the links between mutant GOF-p53 and lung cancers are not well established. In the present study, we set to examine how we can better sensitize resistant GOF-p53 lung cancer cells through modulation of cellular protein degradation machineries, proteasome and autophagy. H1299 p53 null lung cancer cells were stably transfected with R273H mutant GOF-p53 or wild-type (wt) p53 or empty vectors. The presence of R273H-P53 conferred the cancer cells with drug resistance not only against the widely used chemotherapeutic agents like cisplatin (CDDP) or 5-flurouracil (5-FU) but also against potent alternative modes of therapy like proteasomal inhibition. Therefore, there is an urgent need for new strategies that can overcome GOF-p53 induced drug resistance and prolong patient survival following failure of standard therapies. We observed that the proteasomal inhibitor, peptide aldehyde N-acetyl-leu-leu-norleucinal (commonly termed as ALLN), caused an activation of cellular homeostatic machinery, autophagy in R273H-P53 cells. Interestingly, inhibition of autophagy by chloroquine (CQ) alone or in combination with ALLN failed to induce enhanced cell death in the R273H-P53 cells; however, in contrast, an activation of autophagy by serum starvation or rapamycin increased sensitivity of cells to ALLN-induced cytotoxicity. An activated autophagy was associated with increased ROS and ERK signaling and an inhibition of either ROS or ERK signaling resulted in reduced cytotoxicity. Furthermore, inhibition of GOF-p53 was found to enhance autophagy resulting in increased cell death. Our findings provide novel insights pertaining to mechanisms by which a GOF-p53 harboring lung cancer cell is better sensitized, which can lead to the development of advanced therapy against resistant lung cancer cells.
Biosynthesized Protein-Capped Silver Nanoparticles Induce ROS-Dependent Proapoptotic Signals and Prosurvival Autophagy in Cancer Cells
(ACS, 2017) Panwar, Jitendra; Rahaman, Inamur; Chowdhury, Rajdeep
In recent years, the use of silver nanoparticles (AgNPs) in biomedical applications has shown an unprecedented boost along with simultaneous expansion of rapid, high-yielding, and sustainable AgNP synthesis methods that can deliver particles with well-defined characteristics. The present study demonstrates the potential of metal-tolerant soil fungal isolate Penicillium shearii AJP05 for the synthesis of protein-capped AgNPs. The particles were characterized using standard techniques, namely, UV–visible spectroscopy, transmission electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The anticancer activity of the biosynthesized AgNPs was analyzed in two different cell types with varied origin, for example, epithelial (hepatoma) and mesenchymal (osteosarcoma). The biological NPs (bAgNPs) with fungal-derived outer protein coat were found to be more cytotoxic than bare bAgNPs or chemically synthesized AgNPs (cAgNPs). Elucidation of the molecular mechanism revealed that bAgNPs induce cytotoxicity through elevation of reactive oxygen species (ROS) levels and induction of apoptosis. Upregulation of autophagy and activation of JNK signaling were found to act as a prosurvival strategy upon bAgNP treatment, whereas ERK signaling served as a prodeath signal. Interestingly, inhibition of autophagy increased the production of ROS, resulting in enhanced cell death. Finally, bAgNPs were also found to sensitize cells with acquired resistance to cisplatin, providing valuable insights into the therapeutic potential of bAgNPs. To the best of our knowledge, this is the first study that provides a holistic idea about the molecular mechanisms behind the cytotoxic activity of protein-capped AgNPs synthesized using a metal-tolerant soil fungus.
Cancer: an evolutionary perspective
(Sci Medical, 2015) Chowdhury, Rajdeep; Mukherjee, Sudeshna
Cancer is intricately linked to our evolutionary history. The origin and progression of cancer can hence be better understood when viewed from an evolutionary perspective. In this review, we portray the fundamental fact that within the complex ecosystem of the human body, the cancerous cells also evolve. Just like any organism, they face diverse selective pressure to adapt to the tumor environment. There exists a competitive struggle that eliminates the unfit, leaving the well-adapted to thrive. Sequential acquisition of “driver mutations”, chromosomal instability triggering macromutations and punctuated bursts of genetic changes can all hypothetically contribute to the origin and evolution of cancer. We further describe that like in any ecosystem, cancer evolution involves not just the cancerous cells but also its interaction with the environment. However, as cancer evolves, individual cells behave more like a unicellular organism focused on its own survival. We also discuss evidences where cancer has evolved through transmission between individuals. An evolutionary analogy can open up new vistas in the treatment of this dreadful disease
Chitosan-encapsulated ZnS : M (M: Fe3+ or Mn2+) quantum dots for fluorescent labelling of sulphate-reducing bacteria
(IAS, 2016) Chowdhury, Rajdeep; MAZUMDER, Sonal
Chitosan-encapsulated Mn2+andFe^{3+}−dopedZnScolloidalquantumdots(QDs)weresynthesizedusingchemicalprecipitationmethod.Thoughtherearemanyreportsonbio−imagingapplicationsofZnSQDs,thepresentstudyfocussedonthenewtypeofmicrobial−inducedcorrosivebacteriaknownassulphate−reducingbacteria,Thiobacillusnovellus.Sulphate−reducingbacteriacanobtainenergybyoxidizingorganiccompoundswhilereducingsulphatestohydrogensulphide.Thiscancreateaprobleminengineeringindustries.Whenmetalsareexposedtosulphatecontainingwater,waterandmetalinteractsandcreatesalayerofmolecularhydrogenonthemetalsurface.Sulphate−reducingbacteriathenoxidizethehydrogenwhilecreatinghydrogensulphide,whichcontributestocorrosionforinstance,inpipelinesofoilandgasindustries.Inthisstudy,detectionandlabellingofsulphate−reducingbacteriaisdemonstratedusingfluorescentQDs.ChitosancappedZnSQDsweresynthesizedusingdopantsatdifferentdopingconcentrations.UV–Visspectroscopy,XRDandFTIRcharacterizationsweredonetoidentifytheopticalbandgapenergy,crystalplanesanddeterminethepresenceofcappingagent,respectively.Themorphologyandtheaverageparticlesizeof3.5\pm 0.2$ nm were analysed using TEM which substantiated UV–Vis and XRD results. Photoluminescence spectroscopy detected the bacteria attachment to the QDs by showing significant blue shift in bacteria conjugated ZnS QDs. Fluorescence microscopy confirmed the fluorescent labelling of QDs to Thiobacillus novellus bacteria cells making them ideal for bio-labelling applications.
Chloroquine attenuates hypoxia-mediated autophagy to curb thrombosis- an ex vivo and in vivo study
(2024-04) Mukherjee, Sudeshna; Majumder, Syamantak; Chowdhury, Shibasish; Chowdhury, Rajdeep
Hypoxia can trigger the activation of blood platelets, leading to thrombosis. If not addressed clinically, it can cause severe complications and fatal consequences as well. The current treatment regime for thrombosis is often palliative and includes long-term administration of anticoagulants, which has the risk of over-bleeding in injury and other secondary effects as well. This demands a deeper understanding of the process and exploration of an alternative therapeutic avenue. Interestingly, recent studies demonstrate that platelets though atypical and enucleated, possess components of autophagy machinery. This cellular homeostatic process though well-studied in non-platelet cells, is under-explored in platelets.
Chloroquine induces transitory attenuation of proliferation of human lung cancer cells through regulation of mutant P53 and YAP
(Springer, 2022-11) Chowdhury, Shibasish; Chowdhury, Rajdeep; Mukherjee, Sudeshna
Non-small cell lung carcinoma (NSCLC) is the most common cause of cancer-associated deaths worldwide. Though recent development in targeted therapy has improved NSCLC prognosis, yet there is an unmet need to identify novel causative factors and appropriate therapeutic regimen against NSCLCs.
Cisplatin-induced oxidative stress regulates YAP to modulate epigenome promoting survival of osteosarcoma cells
(2025-08) Chowdhury, Rajdeep; Chowdhury, Shibasish; Mukherjee, Sudeshna
The widely used chemotherapeutic drug cisplatin (CDDP) is an integral part of the pre-operative chemotherapy protocol for high-grade osteosarcoma (OS). However, despite an aggressive treatment regimen, drug refractoriness is a major hindrance to successful therapy. We previously identified key transcriptomic alterations essential for the survival of OS cells following CDDP exposure. In the present study, we further demonstrate that CDDP treatment resulted in a ROS-dependent enrichment of the repressive histone mark H3K27me3 at the upstream promoter regions of growth-promoting genes such as CCNA2, and on the promoter of the negative regulator of Yes-Associated Protein (YAP)-LATS1, thereby contributing to their transcriptional repression. This was associated with a growth arrest, and quenching of ROS with N-acetyl cysteine (NAC) reversed it. Importantly, repression of LATS1 led to an increased nuclear localization of YAP, while pharmacological or genetic ablation of YAP reduced CDDP-mediated induction of repressive marks. YAP was further found to co-localize and co-immunoprecipitate with the Polycomb Repressive Complex 2 (PRC2) catalytic member-the histone methyl transferase-EZH2, indicating its putative role in mediating transcriptional repression. In lieu of the above, inhibition of YAP or reversal of the repressive chromatin state using a histone deacetylase (HDAC) inhibitor sensitized OS cells to a low-dose CDDP treatment as well. Overall, the present study demonstrates an interplay between oxidative stress, epigenetics, and YAP in modulating OS cell fate post CDDP exposure.
Common and Unique microRNAs in Multiple Carcinomas Regulate Similar Network of Pathways to Mediate Cancer Progression
(Springer Nature, 2020) Chowdhury, Rajdeep; Chowdhury, Shibasish; Majumder, Syamantak; Majumder, Syamantak
Cancer is a complex disease with a fatal outcome. Early detection of cancer, by monitoring appropriate molecular markers is very important for its therapeutic management. In this regard, the short non-coding RNA molecules, microRNAs (miRNAs) have shown great promise due to their availability in circulating fluids facilitating non-invasive detection of cancer. In this study, an in silico comparative analysis was performed to identify specific signature miRNAs dysregulated across multiple carcinomas and simultaneously identify unique miRNAs for each cancer type as well. The miRNA-seq data of cancer patient was obtained from GDC portal and their differential expressions along with the pathways regulated by both common and unique miRNAs were analyzed. Our studies show twelve miRNAs commonly dysregulated across seven different cancer types. Interestingly, four of those miRNAs (hsa-mir-210, hsa-mir-19a, hsa-mir-7 and hsa-mir-3662) are already reported as circulatory miRNAs (circRNAs); while, the miR-183 cluster along with hsa-mir-93 have been found to be incorporated in exosomes signifying the importance of the identified miRNAs for their use as prospective, non-invasive biomarkers. Further, the target mRNAs and pathways regulated by both common and unique miRNAs were analyzed, which interestingly had significant commonality. This suggests that miRNAs that are commonly de-regulated and specifically altered in multiple cancers might regulate similar pathways to promote cancer. Our data is of significance because we not only identify a set of common and unique miRNAs for multiple cancers but also highlight the pathways regulated by them, which might facilitate the development of future non-invasive biomarkers conducive for early detection of cancers.
Comparison of health effects between individuals with and without skin lesions in the population exposed to arsenic through drinking water in West Bengal, India
(Nature, 2006) Chowdhury, Rajdeep
A study was conducted to explore the effect of arsenic causing conjunctivitis, neuropathy and respiratory illness in individuals, with or without skin lesions, as a result of exposure through drinking water, contaminated with arsenic to similar extent. Exposed study population belongs to the districts of North 24 Parganas and Nadia, West Bengal, India. A total of 725 exposed (373 with skin lesions and 352 without skin lesions) and 389 unexposed individuals were recruited as study participants. Participants were clinically examined and interviewed. Arsenic content in drinking water, urine, nail and hair was estimated. Individuals with skin lesion showed significant retention of arsenic in nail and hair and lower amount of urinary arsenic compared to the group without any skin lesion. Individuals with skin lesion also showed higher risk for conjunctivitis ((odd's ratio) OR: 7.33, 95% CI: 5.05–10.59), peripheral neuropathy (OR: 3.95, 95% CI: 2.61–5.93) and respiratory illness (OR: 4.86, 95% CI: 3.16–7.48) compared to the group without any skin lesion. The trend test for OR of the three diseases in three groups was found to be statistically significant. Again, individuals without skin lesion in the exposed group showed higher risk for conjunctivitis (OR: 4.66, 95% CI: 2.45–8.85), neuropathy (OR: 3.99, 95% CI: 1.95–8.09), and respiratory illness (OR: 3.21, 95% CI: 1.65–6.26) when compared to arsenic unexposed individuals. Although individuals with skin lesions were more susceptible to arsenic-induced toxicity, individuals without skin lesions were also subclinically affected and are also susceptible to arsenic-induced toxicity and carcinogenicity when compared to individuals not exposed to arsenic.
Design, in silico modeling, biodistribution study of rutin and quercetin loaded stable human hair keratin nanoparticles intended for anticancer drug delivery
(IOP, 2018) Chowdhury, Rajdeep; Murugesan, Sankaranarayanan
Current drug development using functional polymers is one of the major tasks for enhancing effectiveness and reducing the side effects in cancer therapeutics. To achieve this immense goal, human hair keratin and model drugs rutin-quercetin (Ru-Qr) were chosen to formulate nanoparticles (NPs). Drug delivery is a core path to produce significant biological activity, and in this connection, the current study was designed to produce highly stable Ru-Qr NPs and their characterization such as the encapsulation of Ru-Qr, the nature, molecular shape, particle size, stability and polydispersity index by Fourier transform infrared spectroscopy, x-ray diffraction, scanning electron microscopy, transmission electron microscopy and Zetasizer analyzer. Based on a literature report, the drug targets 521P and 5P21 were chosen to perform in silico study. The observed in silico study reports showed the strong interaction of NPs and binding pockets of H-Ras P21 proto-oncogene. In this respect, the importance of NPs prompted us to study the biodistribution and in vitro anticancer activity by using cancer cell lines. The investigation of biodistribution showed that it penetrated after 3 d of injection, up to 14% in the liver, 18% in the kidneys, 8% in the spleen, 3% in the heart and 0% in the brain. At 50 μg ml−1 concentration, the NPs displayed 78.02% viability in the normal liver cell line and 95.60% cytotoxicity in the HeLa cell line. The obtained results showed the active NPs enhancing controlled, site-specific drug delivery and they can serve as a novel nanodrug in the management of cancer.
Development of a tumor extracellular pH-responsive nanocarrier by terminal histidine conjugation in a star shaped poly(lactic-co-glycolic acid)
(Elsiever, 2021) Chowdhury, Rajdeep; Roy, Aniruddha
After reaching the tumor site, nanoparticles (NPs) mostly accumulate in the periphery of the tumor, as their intra-tumoral penetration is prevented due to the low perfusion, high interstitial fluid pressure, and dense matrix present in the tumor. A pH-responsive carrier can improve tumor permeation by releasing the drug quickly in the acidic tumor pH, helping its uniform tumor distribution through diffusion. In the current study, we have developed a histidine modified star-shaped PLGA (sPLGA-His) for the tumor-targeted delivery of the drug combination of docetaxel and disulfiram. The sPLGA-His NPs exhibited a rapid pH-responsive drug release behavior, with significantly increased drug release at pH 6.5 compared to pH 7.4 in 12 h. In-vitro cytotoxicity analysis showed that the pH-sensitive sPLGA-His NPs had enhanced efficacy in both 2D and 3D cell culture models. In the cell uptake study, the sPLGA-His NPs exhibited endosomal escape and uniform cellular distribution, whereas sPLGA NPs were found to be accumulated in the endosomes. In the tumor spheroid model, deep penetration was observed with the sPLGA-His NPs, while sPLGA NPs were found to be accumulated in the periphery. Using fluorescent colocalization as well as FRET analysis, increased release of the encapsulated cargo was noticed with the sPLGA-His NPs, compared to sPLGA NPs. Altogether, the sPLGA-His NPs can be used as a tumor extracellular pH-responsive nanocarrier for efficient drug delivery to the tumor.
Disulfiram potentiates docetaxel cytotoxicity in breast cancer cells through enhanced ROS and autophagy
(Springer, 2020-07) Chowdhury, Rajdeep; Roy, Aniruddha
Recent studies have demonstrated that autophagy plays a critical role in reducing the drug sensitivity of docetaxel (DTX) therapy. Disulfiram (DSF) has exhibited potent autophagy inducing activity in multiple studies. We hypothesized that DSF co-treatment could sensitize breast cancer cells to DTX therapy via autophagy modulation.
Disulfiram potentiates docetaxel cytotoxicity in breast cancer cells through enhanced ROS and autophagy
(Springer, 2020) Chowdhury, Rajdeep; Roy, Aniruddha
Recent studies have demonstrated that autophagy plays a critical role in reducing the drug sensitivity of docetaxel (DTX) therapy. Disulfiram (DSF) has exhibited potent autophagy inducing activity in multiple studies. We hypothesized that DSF co-treatment could sensitize breast cancer cells to DTX therapy via autophagy modulation.