RESUMO
While most patients with early-stage cutaneous T-cell lymphomas (CTCL) have a very good prognosis, the survival of patients with extensive tumour stage and visceral involvement remains extremely poor and necessitates the development of more effective treatment modalities. In this study, we evaluated the in vitro effects of two alkylphosphocholines (APCs, miltefosine and erufosine) and the polyphenolic compound curcumin on 5 human CTCL cell lines (Hut-78, HH, MJ, My-La CD4+ and My-La CD8+). All tested drugs showed considerable cytotoxic activity, as determined by the MTT dye reduction assay. The IC50 values of both APCs ranged from the low micromolar level (Hut-78 cells) to 60-80µM (HH cells). The IC50 values of curcumin ranged from 12 to 24µM. All tested drugs induced apoptosis, as ascertained by morphological changes, DNA fragmentation and activation of caspase cascades. Miltefosine and erufosine induced dephosphorylation of Akt in My-La CD8+ cells and phosphorylation of JNK in Hut-78 and My-La CD8+ cells. APCs increased the level of the autophagic marker LC3B in Hut-78 and MJ cells. Results from co-treatment with autophagy modulators suggested that the cytotoxicity of APCs in CTCL cells is mediated, at least in part, by induction of autophagy.
Assuntos
Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Organofosfatos/farmacologia , Fosforilcolina/análogos & derivados , Compostos de Amônio Quaternário/farmacologia , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Western Blotting , Caspases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Concentração Inibidora 50 , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Linfoma Cutâneo de Células T/metabolismo , Linfoma Cutâneo de Células T/patologia , Proteínas Associadas aos Microtúbulos/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilcolina/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-akt , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
A 73-year-old Caucasian female patient presented for three annular erythematous lesions on the left leg and buttock, persisting for two months, clinically interpreted as erythema annulare centrifugum. Routine laboratory findings were within the normal ranges, Borrelia serology and wet mount microscopy for mycosis were negative. Histologic examination confirmed the diagnosis of superficial erythema annulare centrifugum. Since no association of erythema annulare centrifugum with concomitant bacterial or viral infections, or active systemic disease was found in our patient, we considered the possible activation of her previous breast cancer operated on in October 2000.
