RESUMO
Thyroid carcinogenesis is accompanied by loss of thyroid-specific functions and refractory to radioiodine and thyroid stimulating hormone (TSH) suppression therapy. Redifferentiating agents have been shown to inhibit tumor growth and improve the response to conventional therapy. Polyphenol phytochemicals (PPs) in fruits and vegetables have been reported to inhibit cancer initiation, promotion, progression and induce redifferentiation in selected types. In this study we examined PPs induce redifferentiation in thyroid cancer cell lines. We investigated the effects of genistein, resveratrol, quercetin, kaempferol, and resorcinol on the F9 embryonal carcinoma cell differentiation model. The thyroid cancer cell lines, TPC-1, FTC-133, NPA, FRO, and ARO, displayed growth inhibition in response to genistein, resveratrol, quercetin. We further demonstrated that genistein decreased the dedifferention marker CD97 in NPA cells and resveratrol decreased CD97 in FTC-133, NPA, FRO cells and quercetin decreased CD97 in all cell lines. We observed increased expression of differentiation marker NIS in FTC-133 cells in response to genistein, and resveratrol but no change in NPA, FRO, ARO cells. Quercetin increased or induced NIS in FTC-133, NPA, FRO cells. These findings suggest that PPs may provide a useful therapeutic intervention in thyroid cancer redifferentiation therapy.
Assuntos
Humanos , Antígenos CD/metabolismo , Antineoplásicos/farmacologia , Carcinoma Embrionário/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica , Genisteína/farmacologia , Quempferóis/farmacologia , Modelos Biológicos , Fenóis/farmacologia , Quercetina/farmacologia , Resorcinóis/farmacologia , Estilbenos/farmacologia , Simportadores/metabolismo , Neoplasias da Glândula Tireoide/tratamento farmacológicoRESUMO
PURPOSE: Heat shock proteins (hsps) are molecular chaperones that are synthesized by cells in response to various stress conditions. The expression of hsps have been shown to be associated with carcinogenesis and the expression of hsps have been implicated in the biological behavior of tumors. Recently, hsps have emerged as novel molecular targets in anticancer protocols. The objectives of this study were to investigate the significance of hsp 70/90 in breast carcinogenesis and effect of geldanamycin (a blocker of hsp 90) and quercetin (a blocker of hsp 70) on growth inhibition in different breast cancer cell lines. METHODS: Breast tissues from 82 patients were obtained between June 2003 and May 2005 at the Department of Surgery, Hallym University Hospital. Expression of hsp 70/90 was studied by immunohistochemistry (IHC) on tissue sections from 63 breast carcinomas and 19 benign breast tissues. Both cytoplasmic and nuclear expression was measured. Expression of hsp 70/90 was also analyzed by use of a Western blot with the breast cancer cell lines. We next investigated the effects of blockers of hsp 70/90 on cell growth of the human breast cancer cell lines. RESULTS: More prominent hsp 90 expression was observed in malignant tissue than in benign tissue by both cytoplasmic and nuclear IHC staining (p<0.001, p<0.001). Nuclear hsp 90 expression was associated with a positive lymph node status (p=0.003) and the presence of poorly differentiated tumors (p=0.028). Expression of hsp 70 was not different in malignant and benign tissues as determined by both cytoplasmic and nuclear IHC staining. The breast cancer cell lines all expressed hsp 70/90. Geldanamycin markedly inhibited the cell growth of these breast cancer cell lines in a dosedependent manner and induced apoptosis in the cell lines. Quercetin inhibited cell growth of the cell lines less efficiently. CONCLUSION: The expression of hsp 90 was associated with breast carcinogenesis and the presence of more aggressive tumors. Geldanamycin inhibited cell growth of hsp 90 expressing breast cancer cell lines. We suggest that Hsp 90 may be a possible molecular target against breast cancer.