Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo
Chemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient sa...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-11-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523321001959 |
| _version_ | 1829134274793570304 |
|---|---|
| author | Mark W Nachtigal Paris Musaphir Shiv Dhiman Alon D Altman Frank Schweizer Gilbert Arthur |
| author_facet | Mark W Nachtigal Paris Musaphir Shiv Dhiman Alon D Altman Frank Schweizer Gilbert Arthur |
| author_sort | Mark W Nachtigal |
| collection | DOAJ |
| description | Chemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient samples. l-Rham effectively kills high grade serous ovarian cancer cells grown as 2D or 3D cultures in a dose and time dependent manner. l-Rham efficacy was tested in vivo in a chicken allantoic membrane/COV362 xenograft model, where l-Rham activity was as effective as paclitaxel in reducing tumor weight and metastasis. The efficacy of l-Rham to reduce OVCAR3 tumor xenografts in NRG mice was assessed in low and high tumor burden models. l-Rham effectively reduced tumor formation in the low tumor burden group, and blocked ascites formation in low and high tumor burden animals. l-Rham demonstrates efficacy against OVCAR3 tumor and ascites formation in vivo in NRG mice, laying the foundation for further development of this drug class for the treatment of high grade serous ovarian cancer patients. |
| first_indexed | 2024-12-14T17:57:49Z |
| format | Article |
| id | doaj.art-f1a65bf9ad1c43518cf44ad5fcf60d9f |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-14T17:57:49Z |
| publishDate | 2021-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-f1a65bf9ad1c43518cf44ad5fcf60d9f2022-12-21T22:52:31ZengElsevierTranslational Oncology1936-52332021-11-011411101203Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivoMark W Nachtigal0Paris Musaphir1Shiv Dhiman2Alon D Altman3Frank Schweizer4Gilbert Arthur5Department of Biochemistry and Medical Genetics, University of Manitoba, 301 BMSB-745 Bannatyne Avenu, Winnipeg, Manitoba R3E 0J9, Canada; Department of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba, Winnipeg, Manitoba R3E 0J9, Canada; CancerCare Manitoba Research Institute, Winnipeg, Manitoba R2H 2A6, Canada; Corresponding author at: Department of Biochemistry and Medical Genetics, University of Manitoba, 301 BMSB-745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada.Department of Biochemistry and Medical Genetics, University of Manitoba, 301 BMSB-745 Bannatyne Avenu, Winnipeg, Manitoba R3E 0J9, CanadaDepartment of Chemistry, University of Manitoba, Winnipeg, Manitoba R3T 2N2, CanadaDepartment of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba, Winnipeg, Manitoba R3E 0J9, CanadaDepartment of Chemistry, University of Manitoba, Winnipeg, Manitoba R3T 2N2, CanadaDepartment of Biochemistry and Medical Genetics, University of Manitoba, 301 BMSB-745 Bannatyne Avenu, Winnipeg, Manitoba R3E 0J9, CanadaChemotherapy resistant high grade serous ovarian cancer remains a clinically intractable disease with a high rate of mortality. We tested a novel glycosylated antitumor ether lipid called l-Rham to assess the in vitro and in vivo efficacy on high grade serous ovarian cancer cell lines and patient samples. l-Rham effectively kills high grade serous ovarian cancer cells grown as 2D or 3D cultures in a dose and time dependent manner. l-Rham efficacy was tested in vivo in a chicken allantoic membrane/COV362 xenograft model, where l-Rham activity was as effective as paclitaxel in reducing tumor weight and metastasis. The efficacy of l-Rham to reduce OVCAR3 tumor xenografts in NRG mice was assessed in low and high tumor burden models. l-Rham effectively reduced tumor formation in the low tumor burden group, and blocked ascites formation in low and high tumor burden animals. l-Rham demonstrates efficacy against OVCAR3 tumor and ascites formation in vivo in NRG mice, laying the foundation for further development of this drug class for the treatment of high grade serous ovarian cancer patients.http://www.sciencedirect.com/science/article/pii/S1936523321001959Glycosylated antitumor ether lipid (GAEL)Ovarian cancer patient sample3d spheroidChicken chorioallantoic membrane (cam) modelOVCAR3 xenograft |
| spellingShingle | Mark W Nachtigal Paris Musaphir Shiv Dhiman Alon D Altman Frank Schweizer Gilbert Arthur Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo Translational Oncology Glycosylated antitumor ether lipid (GAEL) Ovarian cancer patient sample 3d spheroid Chicken chorioallantoic membrane (cam) model OVCAR3 xenograft |
| title | Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo |
| title_full | Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo |
| title_fullStr | Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo |
| title_full_unstemmed | Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo |
| title_short | Cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy-resistant high grade serous ovarian cancer in vitro and in vivo |
| title_sort | cytotoxic capacity of a novel glycosylated antitumor ether lipid in chemotherapy resistant high grade serous ovarian cancer in vitro and in vivo |
| topic | Glycosylated antitumor ether lipid (GAEL) Ovarian cancer patient sample 3d spheroid Chicken chorioallantoic membrane (cam) model OVCAR3 xenograft |
| url | http://www.sciencedirect.com/science/article/pii/S1936523321001959 |
| work_keys_str_mv | AT markwnachtigal cytotoxiccapacityofanovelglycosylatedantitumoretherlipidinchemotherapyresistanthighgradeserousovariancancerinvitroandinvivo AT parismusaphir cytotoxiccapacityofanovelglycosylatedantitumoretherlipidinchemotherapyresistanthighgradeserousovariancancerinvitroandinvivo AT shivdhiman cytotoxiccapacityofanovelglycosylatedantitumoretherlipidinchemotherapyresistanthighgradeserousovariancancerinvitroandinvivo AT alondaltman cytotoxiccapacityofanovelglycosylatedantitumoretherlipidinchemotherapyresistanthighgradeserousovariancancerinvitroandinvivo AT frankschweizer cytotoxiccapacityofanovelglycosylatedantitumoretherlipidinchemotherapyresistanthighgradeserousovariancancerinvitroandinvivo AT gilbertarthur cytotoxiccapacityofanovelglycosylatedantitumoretherlipidinchemotherapyresistanthighgradeserousovariancancerinvitroandinvivo |