Department of Biological Sciences

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Author: search.filters.author.Chowdhury, RajdeepSubject: search.filters.subject.Pharmacy

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    Evaluation of Apoptosis and Autophagy Inducing Potential of Berberis aristata, Azadirachta indica, and Their Synergistic Combinations in Parental and Resistant Human Osteosarcoma Cells
    (Frontiers, 2017) Chowdhury, Rajdeep; PAUL, Atish T.; Mukherjee, Sudeshna
    Cancer is a multifactorial disease and hence can be effectively overcome by a multi-constituently therapeutic strategy. Medicinal plant extracts represent a perfect example of such stratagem. However, minimal studies have been done till date that portray the effect of extraction techniques on the phyto-constituent profile of plant extracts and its impact on anticancer activity. In the present study, we have evaluated the anticancer potential of methanolic extracts of Berberis aristata root and Azadirachta indica seeds prepared by various extraction techniques in human osteosarcoma (HOS) cells. Soxhlation extract of B. aristata (BAM-SX) and sonication extract of A. indica (AIM-SO) were most effective in inducing apoptosis in parental drug sensitive, as well as resistant cell type developed by repeated drug exposure. Generation of reactive oxygen species and cell cycle arrest preceded caspase-mediated apoptosis in HOS cells. Interestingly, inhibition of autophagy enhanced cell death suggesting the cytoprotective role of autophagy. Combination studies of different methanolic extracts of BAM and AIM were performed, among which, the combination of BAM-SO and AIM-SO (BAAISO) was found to show synergism (IC50 10.27 µg/ml) followed by combination of BAM-MC and AIM-MC (BAAIMC) with respect to other combinations in the ratio of 1:1. BAAISO also showed synergism when it was added to cisplatin-resistant HOS cells (HCR). Chromatographic profiling of BAM-SX and AIM-SO by high performance thin layer chromatography resulted in identification of berberine (Rf 0.55), palmitine (Rf 0.50) in BAM-SX and azadirachtin A (Rf 0.36), azadirachtin B (Rf 0.56), nimbin (Rf 0.80), and nimbolide (Rf 0.43) in AIM-SO. The cytotoxic sensitivity obtained can be attributed to the above compounds. Our results highlight the importance of extraction technique and subsequent mechanism of action of multi-constituential B. aristata and A. indica against both sensitive and drug refractory HOS cells.
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    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.