Disulfiram and disulfiram-loaded poly-[lactide-co-glycolic acid] nanoparticles modulate metastatic markers and proteasomal activity in hepatocarcinoma Hep3b cell line
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Muddasarul Hoda
Muddasarul Hoda completed his PhD at Pondicherry University, India, in 2016. He is currently working as an assistant professor at the Department of Biological Sciences, Aliah University, Kolkata, India. He has to date published eight research papers. His core research domains include therapeutic nanoparticles, anticancer therapy and phytochemistry. He is currently working on the synergistic behaviour of phytochemicals and its implications in cancer and diabetes.
Bindu Madhuri Cavuturu is a PhD scholar at the Department Of Biotechnology, Pondicherry University, Puducherry, India. Her core research area includes ‘Drug designing ’ through bioprospecting of natural sources with an intended focus towards the cancer. She received her MSc degree in Bio-medical Genetics at the Vellore Institute of Technology, Vellore, India, in 2011. She has also specialised in computational biology with respective to the docking and simulation studies with focus on protein-ligand interaction.
Saleem Iqbal is pursuing a PhD in Structural Biology at the Department of Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, India. He received his MSc degree in Bioinformatics at the University of Madras in the year 2013. His research interests are structural biology, molecular dynamics and simulation, protein crystallography and systems biology.
Garima Shakya, PhD, is an assistant professor at the Department of Biochemistry, Idhaya College of Arts and Science for Women, Puducherry, India. Dr. Garima has published 14 research papers in various international journals and presented her research findings at several national and international conferences. She has cleared UGC/CSIR JRF (India) in 2010. Her research interests include cancer biology and phytotherapy research.
Rukkumani Rajagopalan is an assistant professor at the Department of Biochemistry and Molecular Biology, Pondicherry University, India. She completed her PhD in 2005 at Annamalai University, India. She is an active researcher with more than 50 research publications to her credit. She has successfully guided five PhD scholars and a number of MSc students. Her core area of interest includes phytomedicine, nanobiotechnology, cancer, diabetes and liver toxicity. She has also successfully completed three national-funded projects in various scientific fields. She is currently working in a collaborative project in the field of nanotechnology and its application in the diagnosis of cancer.
Abstract
Hepatocellular carcinoma (HCC) results in significantly high mortality rates due to its subtle metastatic expressions. Exorbitant costs of anticancer drugs have lead to the concept of repositioning standard drugs for their anticancer potential. One such antialcoholic drug, disulfiram (DSF), has been reported to show significant cytotoxicity (IC50 6 μM) against hepatocarcinoma cells. Hence, we studied its antimetastatic and proteasome-inhibiting potential to ascertain its efficacy against metastatic hepatocarcinoma. In addition, we also studied the influence of the components of polysorbate 80-stabilised poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) on metastastatic markers and proteasome complexes. A significant reduction in antimigratory assays (0.1 μM) and gelatin zymography (0.5 μM) was observed. A Western blot analysis furthermore confirmed the modulation of metastatic markers. Chymotrypsin-like activity was significantly inhibited at 2 μM of DSF, and in silico docking studies show comparable gliding scores of DSF against standard antimetastatic drugs. Our experiments suggest a significant antimetastatic and proteasome-inhibiting potential of DSF and its loaded NPs. We also infer that polysorbate 80 and PLGA neither show interference with drug behaviour nor inhibit metastasis and proteasome activity, thus behaving as components of a neutral vector. However, they may potentially manipulate the pharmacokinetics of DSF for achieving maximum therapeutic efficacy, in addition to targeted drug delivery.
About the authors
Muddasarul Hoda completed his PhD at Pondicherry University, India, in 2016. He is currently working as an assistant professor at the Department of Biological Sciences, Aliah University, Kolkata, India. He has to date published eight research papers. His core research domains include therapeutic nanoparticles, anticancer therapy and phytochemistry. He is currently working on the synergistic behaviour of phytochemicals and its implications in cancer and diabetes.
Bindu Madhuri Cavuturu is a PhD scholar at the Department Of Biotechnology, Pondicherry University, Puducherry, India. Her core research area includes ‘Drug designing ’ through bioprospecting of natural sources with an intended focus towards the cancer. She received her MSc degree in Bio-medical Genetics at the Vellore Institute of Technology, Vellore, India, in 2011. She has also specialised in computational biology with respective to the docking and simulation studies with focus on protein-ligand interaction.
Saleem Iqbal is pursuing a PhD in Structural Biology at the Department of Centre of Advanced Study in Crystallography and Biophysics, University of Madras, Chennai, India. He received his MSc degree in Bioinformatics at the University of Madras in the year 2013. His research interests are structural biology, molecular dynamics and simulation, protein crystallography and systems biology.
Garima Shakya, PhD, is an assistant professor at the Department of Biochemistry, Idhaya College of Arts and Science for Women, Puducherry, India. Dr. Garima has published 14 research papers in various international journals and presented her research findings at several national and international conferences. She has cleared UGC/CSIR JRF (India) in 2010. Her research interests include cancer biology and phytotherapy research.
Rukkumani Rajagopalan is an assistant professor at the Department of Biochemistry and Molecular Biology, Pondicherry University, India. She completed her PhD in 2005 at Annamalai University, India. She is an active researcher with more than 50 research publications to her credit. She has successfully guided five PhD scholars and a number of MSc students. Her core area of interest includes phytomedicine, nanobiotechnology, cancer, diabetes and liver toxicity. She has also successfully completed three national-funded projects in various scientific fields. She is currently working in a collaborative project in the field of nanotechnology and its application in the diagnosis of cancer.
Funding: Science and Engineering Research Board, funder ID 10.13039/501100001843, grant no. SB/FT/LS-255/2012.
Conflict of interest statement: The authors state no conflict of interest. All authors have read the journal’s publication ethics and publication malpractice statement available at the journal’s website and hereby confirm that they comply with all its parts applicable to the present scientific work.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- In this issue
- Review
- Endoscopic imaging using surface-enhanced Raman scattering
- Original Articles
- Sodium alginate nanoparticles as a new transdermal vehicle of glucosamine sulfate for treatment of osteoarthritis
- Tailor-made mucoadhesive lipid nanogel improves oromucosal antimycotic activity of encapsulated miconazole nitrate
- Disulfiram and disulfiram-loaded poly-[lactide-co-glycolic acid] nanoparticles modulate metastatic markers and proteasomal activity in hepatocarcinoma Hep3b cell line
Artikel in diesem Heft
- Frontmatter
- In this issue
- Review
- Endoscopic imaging using surface-enhanced Raman scattering
- Original Articles
- Sodium alginate nanoparticles as a new transdermal vehicle of glucosamine sulfate for treatment of osteoarthritis
- Tailor-made mucoadhesive lipid nanogel improves oromucosal antimycotic activity of encapsulated miconazole nitrate
- Disulfiram and disulfiram-loaded poly-[lactide-co-glycolic acid] nanoparticles modulate metastatic markers and proteasomal activity in hepatocarcinoma Hep3b cell line
