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Title: Screening and Identification of Plant Extracts for Inhibiting Lung Cancer Cell Line Expressing Elevated NRF2 Signaling
Researcher: Jayanthi, M K
Guide(s): Subbarao, M V S S T
Keywords: quotLung cancer, Nrf2, Keap1, Anacyclus pyrethrum, Glycyrrhiza glabra, EACquot
University: JSS University
Completed Date: 21/08/2017
Abstract: quotLung cancer is one of the leading causes of deaths due to cancers globally. Even though several therapeutic strategies have been explored for treating advanced malignant lung cancers, the success rate is minimal. Hence, the search for identifying new therapeutic targets and pharmacological agents and drug combinations still continues. Studies have shown the upregulation of Nrf2, a key transcription factor regulating antioxidant genes, in lung cancers and highlighted that targeted inhibition of Nrf2 retard tumor growth in mice. However, not much is known about the relative expression of Nrf2 in well-differentiated, moderately-differentiated and undifferentiated lung tumors. More over, it is also not known whether inhibiting Nrf2 using plant extracts helps in retarding lung tumors in vitro and in vivo. newlineObjective:1. Measure the expression of Nrf2 using IHC in different lung tumor tissues; 2. Screen and identify plant extracts for inhibiting Nrf2 expressing A549 lung cancer cell line; 3. Fractionate and test whether the identified extract inhibit Nrf2 and survival cascades; 4. Assess the efficacy of identified extract for inhibiting the progression of EAC in mice. newline1. Expression of Nrf2 was measured using IHC; 2. Efficacy of plant extracts for inhibiting A549 cells growth was assessed by MTS assay; 3. Nrf2 modulating effect was measured using Nrf2-Keap1 complementary assay, and NQO1 and GST reporter assay; 4. In vivo efficacy of identified extracts assessed using EAC bearing mice. newlineResults of this study showed (a) elevated expression of Nrf2 in poorly differentiated lung tumor tissues; (b) APE and GGE inhibits the A549 lung cancer cells growth with more selectivity; (c) APE and GGE modulate Nrf2 expression and its target genes NQO1 and GST levels in a dose dependent manner; (d) APE and GGE retard the growth of EAC cells in mice and enhance life span. More over, these extracts have protected mice from cisplatin-induced toxicity newlineConclusion:(a) Nrf2 as a good therapeutic target in lung cancers and (b) APE and GGE contain potent Nrf2 modulators. newlinequot newline
Pagination: I-X, 1-93p
Appears in Departments:Medical College

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1-1.4.title.pdfAttached File815.42 kBAdobe PDFView/Open
2-10.pdf1.04 MBAdobe PDFView/Open
i. introduction.pdf710.97 kBAdobe PDFView/Open
i. results.pdf1.61 MBAdobe PDFView/Open
j1.objectives.pdf141.91 kBAdobe PDFView/Open
j. review of literaturedocx.pdf185.57 kBAdobe PDFView/Open
k. materials and methodsdocx.pdf555.16 kBAdobe PDFView/Open
m. discussion.pdf174.5 kBAdobe PDFView/Open
o. conclusion.pdf154.79 kBAdobe PDFView/Open
viva examination and guide and student certificate.pdf841.36 kBAdobe PDFView/Open

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