Abstract | BACKGROUND/AIM: In this study we investigated the effect of DOX and five of its derivatives containing a formamidine group (NCHNRR) at the 3' position with pyrrolidine (DOX-F PYR), piperidine (DOX-F PIP), morpholine (DOX-F MOR), N-methylpiperazine (DOX-F PAZ) and hexamethyleneimine (DOX-F HEX) ring on SKOV-3 ovarian cancer cells. We have focused on the anti-proliferative activity and the value of apoptosis induced by tested analogues. MATERIALS AND METHODS: RESULTS: All of the investigated derivatives were considerably more cytotoxic to the SKOV-3 cell line than DOX. The predominant type of cell death induced by the anthracycline analogues was apoptosis. Necrotic cells represented only a small percentage (<5%) of all cells. The number of apoptotic cells was dependent on the compound and the incubation time. Moreover, a significant increase in caspase-3 activity, DNA fragmentation, and morphological changes in ovarian cells were observed predominantly in new DOX analogues. CONCLUSIONS: All new formamidine derivatives of DOX were effective against ovarian cancer cells. They induced mainly the apoptotic pathway of cell death mediated by caspase-3. The most promising results were obtained for DOX-F MOR and DOX-F PAZ. The least potent was DOX-F HEX.
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Authors | Agnieszka Marczak, Marta Denel-Bobrowska, Aneta Rogalska, Małgorzata Łukawska, Irena Oszczapowicz |
Journal | Environmental toxicology and pharmacology
(Environ Toxicol Pharmacol)
Vol. 39
Issue 1
Pg. 369-83
(Jan 2015)
ISSN: 1872-7077 [Electronic] Netherlands |
PMID | 25561091
(Publication Type: Journal Article)
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Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- Antibiotics, Antineoplastic
- Doxorubicin
- Caspase 3
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Topics |
- Adenocarcinoma
- Antibiotics, Antineoplastic
(pharmacology)
- Apoptosis
(drug effects)
- Caspase 3
- Cell Line, Tumor
- Cell Survival
(drug effects)
- Doxorubicin
(analogs & derivatives, pharmacology)
- Female
- Humans
- Necrosis
(chemically induced)
- Ovarian Neoplasms
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