Advanced search
Start date
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death

Full text
Show less -
Brohem, Carla A. [1] ; Massaro, Renato R. [1] ; Tiago, Manoela [1] ; Marinho, Camila E. [1] ; Jasiulionis, Miriam G. [2] ; de Almeida, Rebeca L. [1] ; Rivelli, Diogo P. [1] ; Albuquerque, Renata C. [1] ; de Oliveira, Tiago F. [1] ; de Melo Loureiro, Ana P. [1] ; Okada, Sabrina [1] ; Soengas, Maria S. [3] ; de Moraes Barros, Silvia B. [1] ; Maria-Engler, Silvya S. [1]
Total Authors: 14
[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin Chem & Toxicol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Pharmacol, Sao Paulo - Brazil
[3] Spanish Natl Canc Res Ctr, Ctr Nacl Invest Oncol, Madrid - Spain
Total Affiliations: 3
Document type: Journal article
Source: PIGMENT CELL & MELANOMA RESEARCH; v. 25, n. 3, p. 354-369, MAY 2012.
Web of Science Citations: 27

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin. (AU)

FAPESP's process: 06/50479-7 - Action of Pothomorphe umbellata extract on the extracellular matrix components in the skin healing process: in vivo and in vitro models
Grantee:Carla Abdo Brohem
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 08/58817-4 - Generation of human artificial skins and invasive melanomas as a platform for pharmacological testing
Grantee:Silvya Stuchi Maria-Engler
Support type: Regular Research Grants
FAPESP's process: 09/54816-6 - Xenobiotic effects in cultured human cells and study of mechanisms of cytotoxic and genotoxic damage
Grantee:Ana Paula de Melo Loureiro
Support type: Regular Research Grants