Relation among oxidative stress, epigenetic alterations and malignant transformation
| Full text | |
| Author(s): |
Melo, Fabiana H. M.
[1]
;
Molognoni, Fernanda
[1, 2]
;
Morais, Alice S.
[2]
;
Toricelli, Mariana
[2]
;
Mouro, Margareth G.
[3]
;
Higa, Elisa M. S.
[3]
;
Lopes, Jose D.
[1]
;
Jasiulionis, Miriam G.
[2, 1]
Total Authors: 8
|
| Affiliation: | [1] Univ Fed Sao Paulo, Disciplina Imunol, BR-04023900 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Disciplina Farmacol, BR-04023900 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Disciplina Nefrol, BR-04023900 Sao Paulo - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Free Radical Biology and Medicine; v. 50, n. 10, p. 1263-1273, MAY 15 2011. |
| Web of Science Citations: | 10 |
| Abstract | |
Melanoma cell lines and cells corresponding to premalignant melanocytes were established by our group after subjecting a nontumorigenic murine melanocyte lineage, melan-a, to sequential cycles of anchorage blockade. Previous results showed that in melan-a cells the superoxide level increases after such procedure. Superoxide production during melanocyte de-adhesion was inhibited by L-sepiapterin, the precursor of eNOS cofactor BH(4), and increased by the inhibitor of BH(4) synthesis, DAHP, hence indicating a partial uncoupling state of eNOS. The eNOS uncoupling seems to be maintained in cells derived from melan-a, because they present decreased nitric oxide and increased superoxide levels. The inhibition of superoxide production in Tm5 melanoma cells with L-sepiapterin reinforces their eNOS-uncoupled state. The maintenance of oxidative stress seems to be important in melanoma apoptosis resistance because Mn(III)TBAP, a superoxide scavenger, or L-sepiapterin renders Tm5 cells more sensitive to anoikis and chemotherapy. More importantly, eNOS uncoupling seems to play a pivotal role in melanocyte malignant transformation induced by sustained anchorage impediment, because no malignant transformation was observed when L-NAME-treated melanocytes were subjected to sequential cycles of de-adhesion. Our results show that uncoupled eNOS contributes to superoxide production during melanocyte anchorage impediment, contributing to anoikis resistance and malignant transformation. (C) 2011 Elsevier Inc. All rights reserved. (AU) | |
| FAPESP's process: | 06/61293-1 - DNA methylation contribution to carcinogenesis |
| Grantee: | Miriam Galvonas Jasiulionis |
| Support type: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 09/03335-8 - Identification of genes that present altered expression due to aberrant promoter methylation in the initial phases of melanoma progression |
| Grantee: | Alice Santana Morais |
| Support type: | Scholarships in Brazil - Master |