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Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH
Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-...
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2021
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| _version_ | 1867613420683001856 |
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| access_status_str | Open Access |
| author | Heikal, Shimaa Adel |
| author_browse | Heikal, Shimaa Adel |
| author_facet | Heikal, Shimaa Adel |
| author_sort | Heikal, Shimaa Adel |
| collection | Thesis |
| description | Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-induced peripheral neuropathy (CIPN) are limiting factors in using these compounds. Using a combination or adjuvant compounds with anti-angiogenic effects is one of the strategies suggested to decrease resistance or ameliorate chemotherapeutic toxicity. The present study investigated the anti-angiogenic effects of Cisplatin and Doxorubicin alone and combined with Sulfated non-anticoagulant heparin (S-NACH), a low molecular weight heparin LMWH that has anti-angiogenic and anti-tumor properties, or OT-515, a tempol congener-derived molecule that might act on inhibiting tumor proliferation and angiogenesis. The compounds' ability to enhance the effects of chemotherapeutic agents and decrease the doses used was tested in-vitro and in-vivo through using a chick chorioallantoic membrane (CAM) model, in the presence and absence, of tumor cells. To elucidate the mechanism of anti-angiogenic effect of the compounds, their impact on endothelial cells was studied by performing cytotoxicity assays using HUVEC and mouse endothelial cells. The results showed that combinations of Cisplatin and Doxorubicin with S-NACH or OT-515 had enhanced anti-tumor and anti-angiogenic effects than individual treatments. This suggests that OT-515 and S-NACH provide promising adjuvant therapy to reduce doses of traditional chemotherapeutic agents and ameliorate their adverse effects. |
| format | Thesis |
| id | oai:fount.aucegypt.edu:etds-2802 |
| institution | American University in Cairo (Egypt) |
| last_indexed | 2026-06-10T12:35:51.500Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from AUC Knowledge Fountain — bepress |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | AUC Knowledge Fountain |
| publisherStr | AUC Knowledge Fountain |
| record_format | dspace |
| source_str | AUC Knowledge Fountain — bepress |
| spelling | oai:fount.aucegypt.edu:etds-2802 Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH Heikal, Shimaa Adel Chemotherapeutic agents have been used for the treatment of numerous types of tumors with great success. Cisplatin and Doxorubicin are among the well-known chemotherapeutic drugs that showed efficacy against various types of cancers. However, cell resistance and major side effects like chemotherapy-induced peripheral neuropathy (CIPN) are limiting factors in using these compounds. Using a combination or adjuvant compounds with anti-angiogenic effects is one of the strategies suggested to decrease resistance or ameliorate chemotherapeutic toxicity. The present study investigated the anti-angiogenic effects of Cisplatin and Doxorubicin alone and combined with Sulfated non-anticoagulant heparin (S-NACH), a low molecular weight heparin LMWH that has anti-angiogenic and anti-tumor properties, or OT-515, a tempol congener-derived molecule that might act on inhibiting tumor proliferation and angiogenesis. The compounds' ability to enhance the effects of chemotherapeutic agents and decrease the doses used was tested in-vitro and in-vivo through using a chick chorioallantoic membrane (CAM) model, in the presence and absence, of tumor cells. To elucidate the mechanism of anti-angiogenic effect of the compounds, their impact on endothelial cells was studied by performing cytotoxicity assays using HUVEC and mouse endothelial cells. The results showed that combinations of Cisplatin and Doxorubicin with S-NACH or OT-515 had enhanced anti-tumor and anti-angiogenic effects than individual treatments. This suggests that OT-515 and S-NACH provide promising adjuvant therapy to reduce doses of traditional chemotherapeutic agents and ameliorate their adverse effects. 2021-09-02T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/1771 https://fount.aucegypt.edu/context/etds/article/2802/viewcontent/Shimaa_Adel_Heikal_Thesis.pdf Theses and Dissertations AUC Knowledge Fountain Angiogenesis Doxorubicin Cisplatin Chick Chorioallantoic Membrane (CAM) OT-515 S-NACH CIPN Biotechnology Neuroscience and Neurobiology Pharmacology, Toxicology and Environmental Health |
| spellingShingle | Angiogenesis Doxorubicin Cisplatin Chick Chorioallantoic Membrane (CAM) OT-515 S-NACH CIPN Biotechnology Neuroscience and Neurobiology Pharmacology, Toxicology and Environmental Health Heikal, Shimaa Adel Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH |
| title | Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH |
| title_full | Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH |
| title_fullStr | Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH |
| title_full_unstemmed | Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH |
| title_short | Anti-angiogenic effects of chemotherapeutic agents and their enhancement with OT-515 and S-NACH |
| title_sort | anti angiogenic effects of chemotherapeutic agents and their enhancement with ot 515 and s nach |
| topic | Angiogenesis Doxorubicin Cisplatin Chick Chorioallantoic Membrane (CAM) OT-515 S-NACH CIPN Biotechnology Neuroscience and Neurobiology Pharmacology, Toxicology and Environmental Health |
| url | https://fount.aucegypt.edu/etds/1771 https://fount.aucegypt.edu/context/etds/article/2802/viewcontent/Shimaa_Adel_Heikal_Thesis.pdf |
| work_keys_str_mv | AT heikalshimaaadel antiangiogeniceffectsofchemotherapeuticagentsandtheirenhancementwithot515andsnach |