Medicine

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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty

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Author: search.filters.author.Thabrew, I.Has files: Yes

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    Biochemistry for clinical medicine
    (Greenwich Medical Media, 2001) Thabrew, I.; Ayling, R. M.; Wicks, C.
    No abstract available
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    In vitro anticancer effect of gedunin on human teratocarcinomal (NTERA-2) cancer stem-like cells
    (Hindawi, 2017) Tharmarajah, L.; Samarakoon, S.R.; Ediriweera, M.K.; Piyathilaka, P.; Thennakoon, K.H.; Senathilake, K.S.; Rajagopalan, U.; Galhena, P.B.; Thabrew, I.
    Gedunin is one of the major compounds found in the neem tree (Azadirachta indica). In the present study, antiproliferative potential of gedunin was evaluated in human embryonal carcinoma cells (NTERA-2, a cancer stem cell model) and peripheral blood mononuclear cells (PBMCs), using Sulforhodamine (SRB) and WST-1 assays, respectively. The effects of gedunin on expression of heat shock protein 90 (HSP90), its cochaperone Cdc37, and HSP client proteins (AKT, ErbB2, and HSF1) were evaluated by real-time PCR. Effects of gedunin on apoptosis were evaluated by (a) apoptosis associated morphological changes, (b) caspase 3/7 expression, (c) DNA fragmentation, (d) TUNEL assay, and (e) real-time PCR of apoptosis related genes (Bax, p53, and survivin). Gedunin showed a promising antiproliferative effect in NTERA-2 cells with IC50 values of 14.59, 8.49, and 6.55 μg/mL at 24, 48, and 72 h after incubations, respectively, while exerting a minimal effect on PBMCs. Expression of HSP90, its client proteins, and survivin was inhibited and Bax and p53 were upregulated by gedunin. Apoptosis related morphological changes, DNA fragmentation, and increased caspase 3/7 activities confirmed the proapoptotic effects of gedunin. Collectively, results indicate that gedunin may be a good drug lead for treatment of chemo and radiotherapy resistant cancer stem cells.
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    Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes with anti- hepatocarcinogenic effects
    (BioMed Central, 2012) Samarakoon, S.R.; Thabrew, I.; Galhena, P.B.; Tennekoon, K.H.
    BACKGROUND A standardized poly-herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes used traditionally in Sri Lanka for cancer therapy has been demonstrated previously, to have anti-hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti-inflammatory activity, and up regulation of p53 and p21 activities are considered to be some of the possible mechanisms through which the above decoction may mediate its anti-hepatocarcinogenic action. The main aim of the present study was to determine whether apoptosis is also a major mechanism by which the decoction mediates its anti-hepatocarcinogenic action. METHODS Evaluation of apoptosis in HepG2 cells was carried out by (a) microscopic observations of cell morphology, (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins associated with cell death. RESULTS The results demonstrated that in HepG2 cells, the decoction can induce (a) DNA fragmentation and (b) characteristic morphological changes associated with apoptosis (nuclear condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The decoction could also, in a time and dose dependent manner, up regulate the expression of the pro-apoptotic gene Bax and down regulate expression of anti-apoptotic Bcl-2 gene (as evident from RT-PCR analysis, immunohistochemistry and western blotting). Further, the decoction significantly (p < .001) enhanced the activities of caspase-3 and caspase-9 in a time and dose dependent manner. CONCLUSIONS Overall findings provide confirmatory evidence to demonstrate that the decoction may mediate its reported anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.
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    Effect of standardized decoction of Nigella sativa seed, Hemidesmusindicus root and Smilax glabra rhizome on the expression of p53 and p21 genes in human hepatoma cells (HepG2) and mouse liver with chemically-induced hepatocarcinogenesis
    (Pharmacotherapy Group, University of Benin, Nigeria, 2012) Samarakoon, S.R.; Thabrew, I.; Galhena, P.B.; Tennekoon, K.H.
    Purpose: To evaluate in vitro (using human hepatoma HepG2 cells) and in vivo (using mouse liver with diethlynitrosamine (DEN)-induced hepatocarcinogenesis) effect of a standardized decoction on the expression of p53 (tumour suppressor) and p21 (cyclin kinase inhibitor) genes with the long-term goal of developing the formulation into a globally acceptable therapy for hepatocellular carcinoma (HCC). Methods: The effect of the decoction on (a) mRNA and (b) protein expression of p53 and p21 genes in HepG2 cells and mouse livers with DEN-induced early hepatocarcinogenesis were evaluated by (a) reverse transcription PCR (RT-PCR) and (b) immunohistochemical and Western blot analysis, respectively. Results: The results demonstrated that the decoction significantly (p < 0.001) enhanced the expression of p53 and p21 genes in a time- and dose-dependent manner in HepG2 cells. A dose of 75 µg/ml significantly increased p53 mRNA at 24 and 48 h and p21 mRNA at 12, 24, 48 h of incubation with the decoction (p < 0.01). Induction of hepatocarcinogenesis in mice significantly increased hepatic expression of both p53 and p21 compared to distilled water control (p < 0.001), while treatment with the decoction further enhanced expression of both genes in DEN-induced hepatocarcinogenesis (p < 0.01). Conclusion: Overall, the findings demonstrate that the decoction may mediate its reported antihepatocarcinogenic effect, at least in part, through the modulating activities of genes involved in tumour suppression and cell cycle arrest.
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    Cytotoxic and apoptotic effect of the decoction of the aerial parts of Flueggea leucopyrus on human endometrial carcinoma (AN3CA) cells
    (Pharmacotherapy Group, University of Benin, Nigeria, 2014) Samarakoon, S.R.; Kotigala, S.B.; Gammana-Liyanage, I.; Thabrew, I.; Tennekoon, K.H.; Siriwardana, A.; Galhena, P.B.
    PURPOSE: To evaluate the anti-cancer potentials of a decoction of Flueggea. leucopyrus (Willd.) on human endometrial carcinoma (AN3CA) cells. METHODS: Decoction was prepared by boiling 60 g of the ground plant material in 1.6 L of distilled water for about 3 h to reduce the volume to 200 mL and then freeze dried. The effect of the decoction on AN3CA cells was determined by evaluating its cytotoxicity by 3-(4, 5-dimethylthiazol-2yl) -2, 5-biphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays, as well as its ability to modulate apoptosis (microscopic observation of morphological changes, DNA fragmentation and caspase activity). The antioxidant activity of the decoction was also determined by DPPH assay, and its total polyphenolic and flavonoid content. RESULTS: The decoction exerted a significant dose-dependent cytotoxicity on AN3CA cells as evident from MTT assay IC50 values of 22.09 and 14.60 µg/mL at 24 and 48 h post-incubation, respectively; and SRB assay IC50 values of 28.60 and 15.09 µg/mL at 24 and 48 h post-incubation, respectively. The decoction also enhanced apoptosis as shown by enhanced DNA fragmentation, microscopic observation of nuclear condensation, fragmentation and apoptotic bodies and enhanced caspase 3 and 9 activities, as well as moderately increased radical scavenging activity. CONCLUSION: The cytotoxic and apoptotic effects demonstrated by F. leucopyrus (Willd.) decoction provide supportive evidence for the ethnomedicinal use of this plant for cancer therapy. Copyright of Tropical Journal of Pharmaceutical Research
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