Carla A Brohem,
Renato R Massaro,
Manoela Tiago,
Camila E Marinho,
Miriam G Jasiulionis,
Rebeca L de Almeida,
Diogo P Rivelli, Renata C Albuquerque,
Tiago F de Oliveira,
Ana P de Melo Loureiro,
Sabrina Okada,
María S Soengas,
Silvia B de Moraes Barros,
Silvya S Maria-Engler
[show abstract]
[hide abstract]
ABSTRACT: 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.
Pigment Cell & Melanoma Research 02/2012; 25(3):354-69. · 5.06 Impact Factor
