Abstract | OBJECTIVE: METHODS: The activity and mechanism of action of lipoplatin were studied in the ME-180 cervical cancer cell line and its cisplatin-resistant clone R-ME-180 and HeLa cells using cell proliferation assays, flow cytometry, ELISA assay, cell migration, spheroids and tumor xenograft. RESULTS: We demonstrated that lipoplatin exhibited a potent antitumoral activity on HeLa, ME-180 cells and its cisplatin-resistant clone R-ME-180. Lipoplatin inhibited cell proliferation in a dose-dependent manner and was more active than the reference drug cisplatin in R-ME-180 cells and induced apoptosis, as evaluated by Annexin-V staining and DNA fragmentation, caspases 9 and 3 activation, Bcl-2, and Bcl-xL down-regulation, but Bax up-regulation inhibited thioredoxin reductase (TrxR) enzymatic activity and increased reactive oxygen species (ROS) accumulation; reduced EGFR expression and inhibited both migration and invasion. R-ME-180, but not ME-180 cells, generated three-dimensional (3D)-multicellular spheroids expressing the cancer stem cell marker ALDH. The ability of R-ME-180 cells to form spheroids in vitro and tumors in nude mice was also remarkably decreased by lipoplatin. CONCLUSIONS:
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Authors | Naike Casagrande, Monica De Paoli, Marta Celegato, Cinzia Borghese, Maurizio Mongiat, Alfonso Colombatti, Donatella Aldinucci |
Journal | Gynecologic oncology
(Gynecol Oncol)
Vol. 131
Issue 3
Pg. 744-52
(Dec 2013)
ISSN: 1095-6859 [Electronic] United States |
PMID | 24029417
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013. |
Chemical References |
- Liposomes
- Reactive Oxygen Species
- lipoplatin
- Aldehyde Dehydrogenase
- Thioredoxin-Disulfide Reductase
- ErbB Receptors
- Cisplatin
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Topics |
- Aldehyde Dehydrogenase
(metabolism)
- Animals
- Apoptosis
(drug effects)
- Cell Growth Processes
(drug effects)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cisplatin
(administration & dosage, pharmacology)
- Drug Resistance, Neoplasm
- ErbB Receptors
(biosynthesis)
- Female
- HeLa Cells
- Humans
- Liposomes
(administration & dosage)
- Mice
- Mice, Nude
- Mitochondria
(drug effects, metabolism)
- Neoplastic Stem Cells
(drug effects, pathology)
- Reactive Oxygen Species
(metabolism)
- Spheroids, Cellular
- Thioredoxin-Disulfide Reductase
(antagonists & inhibitors, metabolism)
- Uterine Cervical Neoplasms
(drug therapy, metabolism, pathology)
- Xenograft Model Antitumor Assays
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