Abstract | BACKGROUND: OBJECTIVES: METHODS:
Melanoma cell lines, two wild types and two with dysfunctional p53 derived from one of them were used. The mechanism of anti-proliferative and pro-apoptotic effects and the effect on DNA was investigated using MTT assay, flow cytometry, Western blot analysis, fluorescence and electron microscopy. RESULTS: All tested alkaloids exhibit strong anti-proliferative activity. CHL, CHE and SA induced apoptosis, which was probably mediated by decreasing levels of anti-apoptotic proteins (Bcl-xL, Mcl-1, XIAP) and was accompanied by mitochondrial membrane potential decrease as well as caspase-3 and PARP cleavage. Although all alkaloids caused DNA damage, which was demonstrated by induction of H2AX phosphorylation, none of the tested alkaloids stabilised p53 and their toxicity in cells with non-functional p53 was comparable to wild type cells. CONCLUSION: Despite the profound similarity of BAs molecular structures, it is clear that the mechanism of cell death induction is different for each alkaloid. Our results indicate that BAs could be effective in malignant melanoma treatment, including tumours which have lost wild type p53.
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Authors | Jindřiška Hammerová, Stjepan Uldrijan, Eva Táborská, Iva Slaninová |
Journal | Journal of dermatological science
(J Dermatol Sci)
Vol. 62
Issue 1
Pg. 22-35
(Apr 2011)
ISSN: 1873-569X [Electronic] Netherlands |
PMID | 21324654
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Alkaloids
- Amino Acid Chloromethyl Ketones
- Benzophenanthridines
- Tumor Suppressor Protein p53
- benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
- DNA
- Caspases
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Topics |
- Alkaloids
(chemistry, metabolism, pharmacology)
- Amino Acid Chloromethyl Ketones
(pharmacology)
- Apoptosis
- Benzophenanthridines
(pharmacology)
- Caspases
(metabolism)
- Cell Proliferation
- Cell Survival
- DNA
(metabolism)
- DNA Damage
- Genes, p53
- Humans
- Melanoma
(genetics, metabolism)
- Models, Biological
- Models, Chemical
- Skin Neoplasms
(genetics, metabolism)
- Tumor Suppressor Protein p53
(metabolism)
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