OBJECTIVE: To characterize the molecular pathways involved in apoptosis following administration of histone deacetylase inhibitors to Type I and II endometrial cancer cells. METHODS: Ark2, Ishikawa, and AN3 cell lines representing both Type I and II endometrial cancers were treated with various concentrations of oxamflatin and HDAC inhibitor-1. Cell apoptosis was determined by flow cytometry, nuclear staining, Western blotting, and mitochondrial membrane potential assays. RESULTS: Compared to controls, there was a 95% reduction in the growth of Ark2 cells following administration of histone deacetylase inhibitors and this response was dose-dependent. These agents also caused profound morphologic changes and loss of mitochondrial membrane potentials consistent with the induction of apoptosis. Cleavage of PARP, caspase-9, and caspase-8 was detected, confirming the activation of apoptotic cascades in endometrial carcinoma cells. This effect was present in both serous and endometrioid cell types. CONCLUSION: Our results suggest that oxamflatin and HDAC inhibitor-1 have potent cytotoxicity in endometrial cancer cells by inducing cell apoptosis. Histone deacetylase inhibitors are promising agents for the treatment of both Type I and II endometrial carcinoma.
OBJECTIVE: To characterize the molecular pathways involved in apoptosis following administration of histone deacetylase inhibitors to Type I and II endometrial cancer cells. METHODS:Ark2, Ishikawa, and AN3 cell lines representing both Type I and II endometrial cancers were treated with various concentrations of oxamflatin and HDAC inhibitor-1. Cell apoptosis was determined by flow cytometry, nuclear staining, Western blotting, and mitochondrial membrane potential assays. RESULTS: Compared to controls, there was a 95% reduction in the growth of Ark2 cells following administration of histone deacetylase inhibitors and this response was dose-dependent. These agents also caused profound morphologic changes and loss of mitochondrial membrane potentials consistent with the induction of apoptosis. Cleavage of PARP, caspase-9, and caspase-8 was detected, confirming the activation of apoptotic cascades in endometrial carcinoma cells. This effect was present in both serous and endometrioid cell types. CONCLUSION: Our results suggest that oxamflatin and HDAC inhibitor-1 have potent cytotoxicity in endometrial cancer cells by inducing cell apoptosis. Histone deacetylase inhibitors are promising agents for the treatment of both Type I and II endometrial carcinoma.
Authors: M S Soengas; P Capodieci; D Polsky; J Mora; M Esteller; X Opitz-Araya; R McCombie; J G Herman; W L Gerald; Y A Lazebnik; C Cordón-Cardó; S W Lowe Journal: Nature Date: 2001-01-11 Impact factor: 49.962
Authors: Y Terao; J Nishida; S Horiuchi; F Rong; Y Ueoka; T Matsuda; H Kato; Y Furugen; K Yoshida; K Kato; N Wake Journal: Int J Cancer Date: 2001-10-15 Impact factor: 7.396
Authors: G L Mutter; M C Lin; J T Fitzgerald; J B Kum; J P Baak; J A Lees; L P Weng; C Eng Journal: J Natl Cancer Inst Date: 2000-06-07 Impact factor: 13.506
Authors: L M Butler; D B Agus; H I Scher; B Higgins; A Rose; C Cordon-Cardo; H T Thaler; R A Rifkind; P A Marks; V M Richon Journal: Cancer Res Date: 2000-09-15 Impact factor: 12.701
Authors: M S Kim; H J Kwon; Y M Lee; J H Baek; J E Jang; S W Lee; E J Moon; H S Kim; S K Lee; H Y Chung; C W Kim; K W Kim Journal: Nat Med Date: 2001-04 Impact factor: 53.440
Authors: Sanjib Chowdhury; Gillian M Howell; Carol A Teggart; Aparajita Chowdhury; Jonathan J Person; Dawn M Bowers; Michael G Brattain Journal: J Biol Chem Date: 2011-07-08 Impact factor: 5.157