Publications by authors named "B T Prabhakar"

349 Publications

Antiproliferative pharmacophore azo-hydrazone analogue BT-1F exerts death signalling pathway targeting STAT3 in solid tumour.

Pharmacol Rep 2022 Jan 10. Epub 2022 Jan 10.

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka, 577203, India.

Background: Anomalous activation of intra-cellular signalling cascades confers neoplastic properties on malignant cells. The JAK2/STAT3 proteins play a pivotal role in the pathogenesis of most of the solid malignancies. The over expression of STAT3 in these tumours results in an evasion of apoptosis and thereby pathogenesis. Hence, strategy to target STAT3 to regress tumour development is an emerging new concept. As an approach, anti-neoplastic drug, Azo-hydrozone analogue, BT-1F with potential anti-proliferative effect was evaluated to demonstrate its capacity to counteract STAT3 signal with mechanistic approach.

Methods: Cell based screening for cytotoxicity was performed through MTT, LDH and Trypan blue. The BT-1F induced anti-clonogenic property by clonogenic assay. The apoptotic capacity was examined by crystal violet staining, flow cytometry, Annexin-FITC, DAPI and TUNEL assay. The altered signalling events were studied using immunoblot. The drug-induced anti-tumour effect was evaluated in an in-vivo solid tumour model and molecular interaction was further validated by in-silico studies.

Results: The BT-1F exerts chemo-sensitivity specifically against EAC and A549 cells without altering its normal counterpart. The anti-proliferative/anti-clonogenic effect was due to the induction of apoptosis through inhibition of STAT3 signal. Eventually downstream signalling proteins p53, Bax, Bad and Bcl-xL were significantly altered. Further in-vivo experimental results validated  in-vitro findings. The computational approaches assures the BT-1F efficiency in binding with STAT3.

Conclusion: Systemic validation of STAT3 target drug, BT-1F in in-vitro, in-silico and in-vivo models has promising strategy for solid cancer treatment.
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http://dx.doi.org/10.1007/s43440-021-00345-wDOI Listing
January 2022

3D Printed Personalized Medicine for Cancer: Applications for Betterment of Diagnosis, Prognosis and Treatment.

AAPS PharmSciTech 2021 Dec 1;23(1). Epub 2021 Dec 1.

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Vile Parle (West), Mumbai, India.

Cancer treatment is challenging due to the tumour heterogeneity that makes personalized medicine a suitable technique for providing better cancer treatment. Personalized medicine analyses patient-related factors like genetic make-up and lifestyle and designs treatments that offer the benefits of reduced side effects and efficient drug delivery. Personalized medicine aims to provide a holistic way for prevention, diagnosis and treatment. The customization desired in personalized medicine is produced accurately by 3D printing which is an established technique known for its precision. Different 3D printing techniques exhibit their capability in producing cancer-specific medications for breast, liver, thyroid and kidney tumours. Three-dimensional printing displays major influence on cancer modelling and studies using cancer models in treatment and diagnosis. Three-dimensional printed personalized tumour models like physical 3D models, bioprinted models and tumour-on-chip models demonstrate better in vitro and in vivo correlation in drug screening, cancer metastasis and prognosis studies. Three-dimensional printing helps in cancer modelling; moreover, it has also changed the facet of cancer treatment. Improved treatment via custom-made 3D printed devices, implants and dosage forms ensures the delivery of anticancer agents efficiently. This review covers recent applications of 3D printed personalized medicine in various cancer types and comments on the possible future directions like application of 4D printing and regularization of 3D printed personalized medicine in healthcare.
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http://dx.doi.org/10.1208/s12249-021-02153-0DOI Listing
December 2021

Anti-neoplastic pharmacophore benzophenone-1 coumarin (BP-1C) targets JAK2 to induce apoptosis in lung cancer.

Apoptosis 2021 Nov 27. Epub 2021 Nov 27.

Molecular Biomedicine Laboratory, Postgraduate Department of Studies and Research in Biotechnology, Sahyadri Science College, Kuvempu University, Shivamogga, Karnataka, 577203, India.

Reigning of the abnormal gene activation associated with survival signalling in lung cancer leads to the anomalous growth and therapeutic failure. Targeting specific cell survival signalling like JAK2/STAT3 nexus has become a major focus of investigation to establish a target specific treatment. The 2-bromobenzoyl-4-methylphenoxy-acetyl hydra acetyl Coumarin (BP-1C), is new anti-neoplastic agent with apoptosis inducing capacity. The current study was aimed to develop antitumor phramacophore, BP-1C as JAK2 specific inhibitor against lung neoplastic progression. The study validates and identifies the molecular targets of BP-1C induced cell death. Cell based screening against multiple cancer cell lines identified, lung adenocarcinoma as its specific target through promotion of apoptosis. The BP-1C is able to induce, specific hall marks of apoptosis and there by conferring anti-neoplastic activity. Validation of its molecular mechanism, identified, BP-1C specifically targets JAK2 phosphorylation, and inhibits its downstream STAT3 signalling pathway to induce cell death. As a consequence, modulation in Akt/Src survival signal and altered expression of interwoven apoptotic genes were evident. The results were reproducible in an in-vivo LLC tumor model and in-ovo xenograft studies. The computational approaches viz, drug finger printing confers, BP-1C as novel class JAK2 inhibitor and molecular simulations studies assures its efficiency in binding with JAK2. Overall, BP-1C is a novel JAK2 inhibitor with experimental evidence and could be effectively developed into a promising drug for lung cancer treatment.
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http://dx.doi.org/10.1007/s10495-021-01699-5DOI Listing
November 2021

Quercetin-loaded platelets as a potential targeted therapy for glioblastoma multiforme cell line U373-MG.

Biotechnol J 2021 Dec 12;16(12):e2100271. Epub 2021 Oct 12.

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai, Maharashtra, India.

Over the globe, the incidence of glioblastoma multiforme (GM) is very low, that is, 1-4 cases per 100,000, but it is fatal and cancer grows very fast inside the brain tissues, namely astrocytes and oligodendrocytes. Because of the rapid growth, it is difficult to halt the dissemination of tumor in adjacent tissues. Although temozolomide (TMZ) is a currently approved standard of care, it develops resistance over the period. Therefore, there is a need to develop a novel drug delivery system. In this work, authors have developed platelets as drug delivery carriers-loaded with quercetin (QCT) for targeting GM. The effect of QCT and QCT-platelet was assessed on the U373-MG cell line. Natural human platelets were used as carriers for drug loading and drug delivery. Platelets possess an open canalicular system that allows the uptake of drug molecules in the platelet cytoplasm. The study showed that the maximum encapsulation efficiency of QCT-platelet was 93.96 ± 0.12% and the maximum drug release in 24 h was 76.26 ± 0.13% in-vitro at pH 5.5 that mimics the tumor microenvironment. In this work, there is a three-fold enhancement of solubility of QCT. The cytotoxic activity of QCT-platelets was studied in the U373-MG human astrocytoma glioblastoma cell line and the cell viability was 14.52 ± 1.53% after 48 h. Thus, platelets were proved as good carriers for therapeutic moieties and can be effectively used to target the glioblastoma tumor in the near future.
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http://dx.doi.org/10.1002/biot.202100271DOI Listing
December 2021

Strategies for the delivery of antidiabetic drugs via intranasal route.

Int J Pharm 2021 Oct 1;608:121068. Epub 2021 Sep 1.

Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM'S NMIMS, V.L. Mehta Road, Vile Parle (W), Mumbai, India. Electronic address:

Diabetes is a metabolic disorder defined by higher blood glucose levels in the body generally controlled by antidiabetic agents (oral) and insulin (subcutaneous). To avoid the limitations of the conventional routes such as lower bioavailability and pain at the site of injection in case of parenteral route modified delivery systems are proposed like transdermal, pulmonary and inhalation delivery and among the other delivery systems nasal drug delivery system that shows the advantages such as reduced frequency of dose, higher patient compliance, safety, ease of administration, prolonged residence time, improved absorption of drug in the body, higher bioavailability and stability. This review article discusses the strategies adopted for the delivery of antidiabetic drugs by the intranasal delivery system. The insulin and glucagon-like peptides on experimentation show results of improved therapeutic levels and patient compliance. The drugs are transported by the paracellular route and absorbed through the epithelial tight junctions successfully by utilising different strategies. The limitations of the nasal delivery such as irritation or burning on administration, degradation by the enzymes, mucociliary clearance, lesser volume of the nasal cavity and permeation through the nasal mucosa. To overcome the challenges different strategies for the nasal administration are studied such as polymers, particulate delivery systems, complexation with peptides and smart delivery using glucose-responsive systems. A vast scope of intranasal preparations exists for antidiabetic drugs in the future for the management of diabetes and more clinical studies are the requirement for the societal impact to battle against diabetes.
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http://dx.doi.org/10.1016/j.ijpharm.2021.121068DOI Listing
October 2021
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