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Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma
Neuroblastoma is the most common type of cancer diagnosed in children aged between one and five years old. Diagnosed children with high-risk neuroblastoma have a 5-year survival rate of approximately 50%. Cisplatin is a commonly used treatment for high-risk neuroblastoma, unfortunately, it is often...
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2025
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| _version_ | 1867613424517644288 |
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| access_status_str | Open Access |
| author | Halawa, Sara Ahmed, Ms |
| author_browse | Halawa, Sara Ahmed, Ms |
| author_facet | Halawa, Sara Ahmed, Ms |
| author_sort | Halawa, Sara Ahmed, Ms |
| collection | Thesis |
| description | Neuroblastoma is the most common type of cancer diagnosed in children aged between one and five years old. Diagnosed children with high-risk neuroblastoma have a 5-year survival rate of approximately 50%. Cisplatin is a commonly used treatment for high-risk neuroblastoma, unfortunately, it is often challenged with chemoresistance due to the induction of autophagy. Autophagy is an interesting cellular pathway that is considered a double-edged sword; it can either enhance apoptosis and suppress tumor progression or promote cell survival thus promoting tumorigenesis.
The current study aimed to explore the role of autophagy inhibition as an adjuvant to chemotherapy on neuroblastoma SK-N-AS cells in vitro. Bafilomycin A-1; 200 nM, was used either as a pretreatment or concurrently with Cisplatin. Cell viability assessment showed that pretreatment with Bafilomycin A1 significantly enhanced cell death of SK-N-AS cells induced by Cisplatin with 82% decrease in cell viability compared to only a 31% decrease with Cisplatin alone. Cell death was further confirmed with flow cytometric analysis of apoptosis, confirming that Bafilomycin A1 pretreatment resulted in a higher percentage of apoptotic cells and induced a G0-G1 phase cell cycle arrest. Furthermore, Bafilomycin A1 pretreatment downregulated mRNA expression of pivotal genes such as ATG7, implying that inhibiting autophagic flux sensitizes neuroblastoma cells to Cisplatin. Additionally, Bafilomycin A1 pretreatment significantly downregulated MYCN, a key chemoresistance driver in high-risk neuroblastoma.
In conclusion, the current findings highlight the use of Bafilomycin A-1 as an adjuvant treatment with chemotherapy as a promising treatment strategy to overcome autophagy-mediated chemoresistance in high-risk neuroblastoma and improve treatment outcomes in pediatric cancer patients. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-3520 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:55.364Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2025 |
| publishDateRange | 2025 |
| publishDateSort | 2025 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-3520 Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma Halawa, Sara Ahmed, Ms Neuroblastoma is the most common type of cancer diagnosed in children aged between one and five years old. Diagnosed children with high-risk neuroblastoma have a 5-year survival rate of approximately 50%. Cisplatin is a commonly used treatment for high-risk neuroblastoma, unfortunately, it is often challenged with chemoresistance due to the induction of autophagy. Autophagy is an interesting cellular pathway that is considered a double-edged sword; it can either enhance apoptosis and suppress tumor progression or promote cell survival thus promoting tumorigenesis. The current study aimed to explore the role of autophagy inhibition as an adjuvant to chemotherapy on neuroblastoma SK-N-AS cells in vitro. Bafilomycin A-1; 200 nM, was used either as a pretreatment or concurrently with Cisplatin. Cell viability assessment showed that pretreatment with Bafilomycin A1 significantly enhanced cell death of SK-N-AS cells induced by Cisplatin with 82% decrease in cell viability compared to only a 31% decrease with Cisplatin alone. Cell death was further confirmed with flow cytometric analysis of apoptosis, confirming that Bafilomycin A1 pretreatment resulted in a higher percentage of apoptotic cells and induced a G0-G1 phase cell cycle arrest. Furthermore, Bafilomycin A1 pretreatment downregulated mRNA expression of pivotal genes such as ATG7, implying that inhibiting autophagic flux sensitizes neuroblastoma cells to Cisplatin. Additionally, Bafilomycin A1 pretreatment significantly downregulated MYCN, a key chemoresistance driver in high-risk neuroblastoma. In conclusion, the current findings highlight the use of Bafilomycin A-1 as an adjuvant treatment with chemotherapy as a promising treatment strategy to overcome autophagy-mediated chemoresistance in high-risk neuroblastoma and improve treatment outcomes in pediatric cancer patients. 2025-02-19T08:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/2474 https://fount.aucegypt.edu/context/etds/article/3520/viewcontent/sara_ahmed_halawa_thesis.pdf Theses and Dissertations AUC Knowledge Fountain Neuroblastoma Bafilomycin A1 Autophagy chemosensitization Biotechnology Cancer Biology Life Sciences Medicine and Health Sciences |
| spellingShingle | Neuroblastoma Bafilomycin A1 Autophagy chemosensitization Biotechnology Cancer Biology Life Sciences Medicine and Health Sciences Halawa, Sara Ahmed, Ms Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma |
| title | Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma |
| title_full | Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma |
| title_fullStr | Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma |
| title_full_unstemmed | Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma |
| title_short | Breaking Down Defenses: Autophagy as a Therapeutic Tool to Enhance Chemosensitivity in Neuroblastoma |
| title_sort | breaking down defenses autophagy as a therapeutic tool to enhance chemosensitivity in neuroblastoma |
| topic | Neuroblastoma Bafilomycin A1 Autophagy chemosensitization Biotechnology Cancer Biology Life Sciences Medicine and Health Sciences |
| url | https://fount.aucegypt.edu/etds/2474 https://fount.aucegypt.edu/context/etds/article/3520/viewcontent/sara_ahmed_halawa_thesis.pdf |
| work_keys_str_mv | AT halawasaraahmedms breakingdowndefensesautophagyasatherapeutictooltoenhancechemosensitivityinneuroblastoma |