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INFLUENCE OF APPLE PEEL EXTRACTS ON ANTIPROLIFERATIVE, INDUCTION OF APOPTOSIS, AND ANTI-METASTASIS ACTIVITIES IN HUMAN BREAST CANCER MDA-MB-231 CELLS UNDER INSULIN-LIKE GROWTH FACTOR 1 TRANSDUCTION PATHWAY

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dc.contributor.authorSair, Ali Tahir
dc.contributor.chairLiu, Ruien_US
dc.contributor.committeeMemberGu, Zhenglongen_US
dc.contributor.committeeMemberGlahn, Raymonden_US
dc.date.accessioned2024-04-05T18:47:49Z
dc.date.issued2023-08
dc.description166 pagesen_US
dc.description.abstractBreast cancer is a highly aggressive and heterogeneous disease with complex features that remains a major health problem and undermines the span and quality of life in women worldwide. Primary literature has shown the role of phenolic compounds in controlling the onset of breast cancer. The mechanism of action of phenolic compounds can be explained by their interaction with signal transduction pathways that regulate cell proliferation and induction of apoptosis.In our study, apple peel extracts were investigated for their potential mechanisms of action against regulating cell proliferation in human breast cancer MDA-MB-231 cells under IGF-1 induction. Apple peel extracts significantly inhibited cellular proliferation in breast cancer cells in a dose-dependent manner at a dose ≥10 mg/mL. The IGF- 1R/PI3K/Akt pathway expression was suppressed by apple peel extracts treatment. Expressions of cyclin D1-stimulating proteins NF-?B and GSK-3? were inhibited, whereas p21 expression was upregulated. Apple peel extracts reduced the expression of cyclin D1, stagnating MDA-MB-231 cells in a G1 cell cycle arrest. Apple peel extracts stimulated PTEN, a tumor suppressor protein and an inhibitor of PI3K/Akt signaling pathway. The results suggested that apple peel extracts can induce inhibitory effects through downregulating IGF-1R/PI3K/Akt signal transduction pathway in human breast cancer MDA-MB-231 cells. In our second project, we investigated the anticancer activities of apple peel phenolic extracts to induce apoptosis in triple negative MDA-MB-231 cells, and we found the following underlying mechanisms. Apple peel extracts inhibited cell proliferation in MDA-MB-231 cells with and without human IGF-1 induction. We showed that Apple peel extracts induced G1/S cell cycle arrest with p53 and p21 upregulation and cyclin D1 downregulation. There were no significant changes in G2/M phase and its regulatory proteins cyclins A2 and B1. The significant inhibitory effects of apple peel extracts were achieved through the downregulation of IGF-1R/PI3K/Akt cascade and promoted mitochondria-mediated apoptosis proteins BAX, Cl-caspase 3, and Cl-caspase 9 and restricted the expression of anti-apoptosis Bcl-2 protein. Triple negative breast cancer has a high tendency of forming metastasis. The objective of our third project was to investigate the anti-metastatic and anti-invasive effect of apple peel extracts on human breast cancer MDA-MB-231 cells through IGF-1 signaling pathway. Apple peel extracts inhibited cell migration in IGF-1-induced MDA- MB-231 cells with the relative wound area under 20 and 30 mg/mL apple peel extracts treatment was 12.07±1.91% and 21.37±1.60%. Apple peel extracts downregulate JAK2(3)/STAT3 activity in human breast cancer MDA-MB-231 cells downregulating JAK2 and JAK3 by 51.07 ± 5.59% and 40.97 ± 3.98% under 30 mg/mL. MMP2 and MMP9 expression was enhanced under IGF-1 inducer, and apple peel extracts was able to reverse the enhanced expression by 33.35 ± 1.76 % and 33.70 ± 4.16 % at 30 mg/mL.en_US
dc.description.embargo2025-09-05
dc.identifier.doihttps://doi.org/10.7298/1288-cm29
dc.identifier.otherSair_cornellgrad_0058F_13733
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:13733
dc.identifier.urihttps://hdl.handle.net/1813/114752
dc.language.isoen
dc.rightsAttribution 4.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/*
dc.subjectApoptosisen_US
dc.subjectApple peel extractsen_US
dc.subjectBreast canceren_US
dc.subjectCell proliferation and metastasisen_US
dc.subjectIGF-1 pathwayen_US
dc.subjectphytochemicalsen_US
dc.titleINFLUENCE OF APPLE PEEL EXTRACTS ON ANTIPROLIFERATIVE, INDUCTION OF APOPTOSIS, AND ANTI-METASTASIS ACTIVITIES IN HUMAN BREAST CANCER MDA-MB-231 CELLS UNDER INSULIN-LIKE GROWTH FACTOR 1 TRANSDUCTION PATHWAYen_US
dc.typedissertation or thesisen_US
dcterms.licensehttps://hdl.handle.net/1813/59810.2
thesis.degree.disciplineFood Science and Technology
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Food Science and Technology

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