2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line
| Format: | General Document |
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| building | INTELEK Repository |
| collection | Online Access |
| collectionurl | https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 |
| copyright | Copyright©PWB2025 |
| country | Malaysia |
| date | 2023-02-01 |
| format | General Document |
| id | 15376 |
| institution | UniSZA |
| internalnotes | Sila masukkan subject wajib Dissertations, Academic. Terima kasih... |
| originalfilename | IMMUNOMODULATORY EFFECTS AND MECHANISMS OF ACTION OF THREE SELECTED FLAVONOIDS ON NK-92 NATURAL KILLER CELL-MEDIATED CYTOTOXICITY AGAINST NCI-H460 LUNG CANCER CELL LINE (PHD_2023).pdf |
| person | Aung Myo Oo |
| recordtype | oai_dc |
| resourceurl | https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15376 |
| sourcemedia | Server storage Scanned document |
| spelling | 15376 https://intelek.unisza.edu.my/intelek/pages/view.php?ref=15376 https://intelek.unisza.edu.my/intelek/pages/search.php?search=!collection3 General Document Malaysia Library Staff (Top Management) Library Staff (Management) Library Staff (Support) Terengganu Faculty of Medicine English application/pdf 1.5 Server storage Scanned document Universiti Sultan Zainal Abidin UniSZA Private Access Universiti Sultan Zainal Abidin SAMBox 2.4.24; modified using iTextSharp™ 5.5.10 ©2000-2016 iText Group NV (AGPL-version) 200 IMMUNOMODULATORY EFFECTS AND MECHANISMS OF ACTION OF THREE SELECTED FLAVONOIDS ON NK-92 NATURAL KILLER CELL-MEDIATED CYTOTOXICITY AGAINST NCI-H460 LUNG CANCER CELL LINE (PHD_2023).pdf 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line 2023-02-01 Aung Myo Oo Flavonoids—Immunological aspects Copyright©PWB2025 Lung cancer is the most prevalent and devastating type of cancer. Although numerous treatment options are available nowadays, lung cancer deaths continue to rise. The adverse effects of chemotherapy and radiotherapy, and the rising rate of recurrence, had persuaded researchers to seek alternative cancer treatment. Cancer immunotherapy, which uses innate immune cells such as T cells and natural killer (NK) cells, has been examined to treat lung cancer. Polyphenolic compounds including flavonoids have the capacity to influence NK cell activity. Evidence suggests that flavonoids, particularly flavone and flavonol, influence anticarcinogenic and pro-apoptotic effects by governing immune cell function, resulting in the suppression of cancer cell growth. Thus, this study was conducted to investigate the immunomodulatory effects of apigenin, luteolin, and quercetin in facilitating the growth of NK-92 cells, on NK-92 cell killing activity against NCI-H460 lung cancer cells, on the secretion of cytotoxic perforin and granulysin granules and type-1 cytokines (interleukin (IL)-2, interferon (IFN)-γ) and type-2 cytokines (IL-4 and IL-10) production. NK-92 cells were cultured in a complete α-Minimum Essential Medium (MEM). Roswell Park Memorial Institute (RPMI) 1640 media was used to culture NCI-H460 lung cancer cells. The cell viability of NK-92 cells treated with apigenin, luteolin, and quercetin (dose range of 6.25 to 400 µg/ml) was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A modified MTT assay was used to test the cytotoxic activity of NK-92 cells against NCI-H460 lung cancer cells. The secretions of perforin and granulysin and cytokines production were then examined using the pre-coated and uncoated sandwich enzyme-linked immunosorbent assay (ELISA) methods, respectively. Apigenin, luteolin, and quercetin all had dose-dependent proliferative effects on NK-92 cell proliferation, with the highest percentage of proliferation found at a dose of 100µg/ml for all three compounds (P <0.05). However, after the 100µg/ml dose, the percentage of cell proliferation gradually decreased. Similarly, at concentrations of 12.5 µg/ml and 25µg/ml, all three tested flavonoids significantly increased NK-cell-mediated cytotoxic activity against lung cancer cells (P < 0.001). The levels of perforin and granulysin secreted by NK cells were significantly increased by apigenin and luteolin treatment but not by quercetin. Luteolin and quercetin treatment were observed to increase NK cell IL-2 secretion significantly. At a 25 µg/ml concentration, luteolin significantly increased NK cells' IFN-γ secretion. Nevertheless, at different doses, all three flavonoid compounds did not affect NK cell type-2 cytokines secretions. Luteolin has the most significant impact on both IL-2 and IFN-γ productions. Apigenin, on the other hand, had no effect on the secretion of type 1 and type 2 cytokines. This study documented that apigenin-treated NK cells exert significant immunomodulatory actions by augmenting proliferation and enhancing cytotoxic activity against lung cancer cell lines via modulating cytotoxic granule secretion whereas luteolin treated-NK cells facilitate both cytotoxic granules and cytokines production. However, quercetin-treated NK cell uses IL-2 production without significantly changing cytotoxic granules secretion for their immunomodulatory action in this study. Overall, it could be deduced that luteolin exerts the strongest immunomodulatory effect and could facilitate NK cell-based cancer therapy. It is meritorious to investigate further these three flavonoids and their effect on immunomodulation in vivo towards lung cancer therapy. Dissertations, Academic Sila masukkan subject wajib Dissertations, Academic. Terima kasih... Flavonoids And Cancer Cell Cytotoxicity Immunomodulatory Mechanisms Of Flavonoids Immune System Modulation By Phytochemicals Thesis |
| spellingShingle | 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line |
| state | Terengganu |
| subject | Flavonoids—Immunological aspects Dissertations, Academic |
| summary | Lung cancer is the most prevalent and devastating type of cancer. Although numerous treatment options are available nowadays, lung cancer deaths continue to rise. The adverse effects of chemotherapy and radiotherapy, and the rising rate of recurrence, had persuaded researchers to seek alternative cancer treatment. Cancer immunotherapy, which uses innate immune cells such as T cells and natural killer (NK) cells, has been examined to treat lung cancer. Polyphenolic compounds including flavonoids have the capacity to influence NK cell activity. Evidence suggests that flavonoids, particularly flavone and flavonol, influence anticarcinogenic and pro-apoptotic effects by governing immune cell function, resulting in the suppression of cancer cell growth. Thus, this study was conducted to investigate the immunomodulatory effects of apigenin, luteolin, and quercetin in facilitating the growth of NK-92 cells, on NK-92 cell killing activity against NCI-H460 lung cancer cells, on the secretion of cytotoxic perforin and granulysin granules and type-1 cytokines (interleukin (IL)-2, interferon (IFN)-γ) and type-2 cytokines (IL-4 and IL-10) production. NK-92 cells were cultured in a complete α-Minimum Essential Medium (MEM). Roswell Park Memorial Institute (RPMI) 1640 media was used to culture NCI-H460 lung cancer cells. The cell viability of NK-92 cells treated with apigenin, luteolin, and quercetin (dose range of 6.25 to 400 µg/ml) was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A modified MTT assay was used to test the cytotoxic activity of NK-92 cells against NCI-H460 lung cancer cells. The secretions of perforin and granulysin and cytokines production were then examined using the pre-coated and uncoated sandwich enzyme-linked immunosorbent assay (ELISA) methods, respectively. Apigenin, luteolin, and quercetin all had dose-dependent proliferative effects on NK-92 cell proliferation, with the highest percentage of proliferation found at a dose of 100µg/ml for all three compounds (P <0.05). However, after the 100µg/ml dose, the percentage of cell proliferation gradually decreased. Similarly, at concentrations of 12.5 µg/ml and 25µg/ml, all three tested flavonoids significantly increased NK-cell-mediated cytotoxic activity against lung cancer cells (P < 0.001). The levels of perforin and granulysin secreted by NK cells were significantly increased by apigenin and luteolin treatment but not by quercetin. Luteolin and quercetin treatment were observed to increase NK cell IL-2 secretion significantly. At a 25 µg/ml concentration, luteolin significantly increased NK cells' IFN-γ secretion. Nevertheless, at different doses, all three flavonoid compounds did not affect NK cell type-2 cytokines secretions. Luteolin has the most significant impact on both IL-2 and IFN-γ productions. Apigenin, on the other hand, had no effect on the secretion of type 1 and type 2 cytokines. This study documented that apigenin-treated NK cells exert significant immunomodulatory actions by augmenting proliferation and enhancing cytotoxic activity against lung cancer cell lines via modulating cytotoxic granule secretion whereas luteolin treated-NK cells facilitate both cytotoxic granules and cytokines production. However, quercetin-treated NK cell uses IL-2 production without significantly changing cytotoxic granules secretion for their immunomodulatory action in this study. Overall, it could be deduced that luteolin exerts the strongest immunomodulatory effect and could facilitate NK cell-based cancer therapy. It is meritorious to investigate further these three flavonoids and their effect on immunomodulation in vivo towards lung cancer therapy. |
| title | 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line |
| title_full | 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line |
| title_fullStr | 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line |
| title_full_unstemmed | 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line |
| title_short | 2023_Immunomodulatory Effects and Mechanisms of Action of Three Selected Flavonoids on Nk-92 Natural Killer Cell-Mediated Cytotoxicity Against Nci-H460 Lung Cancer Cell Line |
| title_sort | 2023_immunomodulatory effects and mechanisms of action of three selected flavonoids on nk-92 natural killer cell-mediated cytotoxicity against nci-h460 lung cancer cell line |