Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are also exploited by IL-24 depending on the cell type. In this work, in vitrostudies were performed to understand the downstream effects of IL-24-mediated ER stress such as eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation, which leads to ternary complex depletion and translation initiation inhibition. We also uncover a novel mechanism of IL-24-mediated ER stress involving the protein kinase A pathway and extrinsic apoptosis in breast cancer cell lines. Finally, we show for the first time that endogenous IL-24 mRNA expression is affected by the differential expression of microRNA-4719 and microRNA-6756-5p incastration-resistant prostate cancer cell lines compared to normal or indolent prostate cancer cell lines. Each chapter of this work uncovers a new mechanism of action that can be applied to the development of anti-cancer therapeutics involving IL-24. Understanding the intricacies of IL-24-mediated apoptosis in different cancer cell line types will contribute to the development of personalized gene therapies that can target tumors in a more safe and non-toxic approach.
","abstract_html":"<p>Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are also exploited by IL-24 depending on the cell type. In this work, <em>in vitro</em>studies were performed to understand the downstream effects of IL-24-mediated ER stress such as eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation, which leads to ternary complex depletion and translation initiation inhibition. We also uncover a novel mechanism of IL-24-mediated ER stress involving the protein kinase A pathway and extrinsic apoptosis in breast cancer cell lines. Finally, we show for the first time that endogenous IL-24 mRNA expression is affected by the differential expression of microRNA-4719 and microRNA-6756-5p incastration-resistant prostate cancer cell lines compared to normal or indolent prostate cancer cell lines. Each chapter of this work uncovers a new mechanism of action that can be applied to the development of anti-cancer therapeutics involving IL-24. Understanding the intricacies of IL-24-mediated apoptosis in different cancer cell line types will contribute to the development of personalized gene therapies that can target tumors in a more safe and non-toxic approach.</p>","abstract_has_math":false,"creators":["Persaud, Leah Eshanie"],"institution":"The Graduate School and University Center of The City University of New York","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Biology","degree_department":null,"school":null,"contributors":[],"advisors":["Moira Sauane"],"committee_chairs":[],"committee_members":["Frida Kleiman","Stephen Redenti","Pablo Peixoto","Eva Sapi"],"year":2019,"date_issued":"2019-05-01T07:00:00Z","date_published":"2019-05-01T07:00:00Z","updated_at":"2026-07-24T02:00:35Z","subjects":["Biology","Cancer Biology","Cell Biology","cancer","therapeutics","ER stress","translation","protein kinase A","microRNA"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://academicworks.cuny.edu/gc_etds/3156","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Moira Sauane"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Frida Kleiman","Stephen Redenti","Pablo Peixoto","Eva Sapi"]},{"key":"dc:creator","label":"Author","values":["Persaud, Leah Eshanie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-04-18T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The Graduate School and University Center of The City University of New York"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Cancer Biology","Cell Biology","cancer","therapeutics","ER stress","translation","protein kinase A","microRNA"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://academicworks.cuny.edu/gc_etds/3156"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are also exploited by IL-24 depending on the cell type. In this work, in vitrostudies were performed to understand the downstream effects of IL-24-mediated ER stress such as eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation, which leads to ternary complex depletion and translation initiation inhibition. We also uncover a novel mechanism of IL-24-mediated ER stress involving the protein kinase A pathway and extrinsic apoptosis in breast cancer cell lines. Finally, we show for the first time that endogenous IL-24 mRNA expression is affected by the differential expression of microRNA-4719 and microRNA-6756-5p incastration-resistant prostate cancer cell lines compared to normal or indolent prostate cancer cell lines. Each chapter of this work uncovers a new mechanism of action that can be applied to the development of anti-cancer therapeutics involving IL-24. Understanding the intricacies of IL-24-mediated apoptosis in different cancer cell line types will contribute to the development of personalized gene therapies that can target tumors in a more safe and non-toxic approach.
"]},{"key":"dc:title","label":"Title","values":["The Molecular Mechanisms Underlying the Cancer Killing Effect of Interleukin-24"]}]}],"canonical_facts":{"dc:contributor.advisor":["Moira Sauane"],"dc:contributor.committeemember":["Frida Kleiman","Stephen Redenti","Pablo Peixoto","Eva Sapi"],"dc:creator":["Persaud, Leah Eshanie"],"dc:date.available":["2019-04-18T07:00:00Z"],"dc:description.abstract":["Interleukin-24 (IL-24) is an immunomodulatory cytokine that also displays specific anti-tumor effects across many cancer cell types. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, metastasis, toxic autophagy, cancer-specific apoptosis, and sensitization to traditional cancer treatments like chemotherapy and radiation. Overexpression of IL-24 can selectively induce apoptosis in various cancer cells while having no adverse effects on normal cells. Due to this favorable killing effect, IL-24 is currently in phase II clinical trials. There is accumulating evidence that IL-24’s anti-cancer activity is primarily through the endoplasmic reticulum (ER) stress pathway but other pathways leading to cell death are also exploited by IL-24 depending on the cell type. In this work, in vitrostudies were performed to understand the downstream effects of IL-24-mediated ER stress such as eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation, which leads to ternary complex depletion and translation initiation inhibition. We also uncover a novel mechanism of IL-24-mediated ER stress involving the protein kinase A pathway and extrinsic apoptosis in breast cancer cell lines. Finally, we show for the first time that endogenous IL-24 mRNA expression is affected by the differential expression of microRNA-4719 and microRNA-6756-5p incastration-resistant prostate cancer cell lines compared to normal or indolent prostate cancer cell lines. Each chapter of this work uncovers a new mechanism of action that can be applied to the development of anti-cancer therapeutics involving IL-24. Understanding the intricacies of IL-24-mediated apoptosis in different cancer cell line types will contribute to the development of personalized gene therapies that can target tumors in a more safe and non-toxic approach.
"],"dc:identifier":["https://academicworks.cuny.edu/gc_etds/3156"],"dc:subject":["Biology","Cancer Biology","Cell Biology","cancer","therapeutics","ER stress","translation","protein kinase A","microRNA"],"dc:title":["The Molecular Mechanisms Underlying the Cancer Killing Effect of Interleukin-24"],"thesis:degree_discipline":["Biology"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["The Graduate School and University Center of The City University of New York"]},"updated_at":"2026-07-24T02:00:35Z"}