kh-1060 and Retinoblastoma

kh-1060 has been researched along with Retinoblastoma* in 1 studies

Other Studies

1 other study(ies) available for kh-1060 and Retinoblastoma

Article	Year
1,25-dihydroxyvitamin D3-induced apoptosis of retinoblastoma cells is associated with reciprocal changes of Bcl-2 and bax. Experimental eye research, 2003, Volume: 77, Issue:1 The active vitamin D metabolite 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and related substances have previously been tested in tissue culture and animal models of retinoblastoma for their use as anti-tumor drugs. However, despite of the potential therapeutic value, the molecular mechanisms through which 1,25-(OH)(2)D(3) inhibits the growth of retinoblastoma cells are incompletely understood. To elucidate possible signalling pathways for the anti-proliferative action of vitamin D compounds in retinal tumor cells, we analyzed the effect of 1,25-(OH)(2)D(3) and its synthetic analogue KH1060 on the growth of human retinoblastoma-derived Y79 cells. Vitamin D receptor (VDR) mRNA was detected by reverse transcription PCR in Y79 cells and in tissue specimens of human retinoblastoma. VDR transcripts were confirmed at the protein level by strong immunostaining of solid retinal tumors for VDR. Incubation with 1,25-(OH)(2)D(3) and KH1060 (10(-10)-10(-6)moll(-1)) decreased the number of Y79 cells in a timely and dose-dependent manner. Treatment with 1,25-(OH)(2)D(3) (10(-10)moll(-1)) for 24 hr caused cell cycle arrest in the G0/1 phase. Apoptosis of Y79 cells in response to 1,25-(OH)(2)D(3) was demonstrated by the means of TdT-dUTP terminal nick-end labelling (TUNEL), annexin V staining, and detection of DNA fragmentation on agarose gels. 1,25-(OH)(2)D(3)-induced programmed death of Y79 cells was accompanied by a concentration-dependent increase in Bax protein and a reduction in Bcl-2 content. These findings suggest that 1,25-(OH)(2)D(3) inhibits the growth of retinoblastoma cells by causing cell cycle arrest and apoptosis. 1,25-(OH)(2)D(3)-induced programmed death of retinoblastoma cells appears to involve reciprocal changes in Bcl-2 and Bax proteins. Topics: Analysis of Variance; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Calcitriol; Cell Cycle; Dose-Response Relationship, Drug; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Interphase; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Calcitriol; Retinal Neoplasms; Retinoblastoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors	2003

Article

Year

1,25-dihydroxyvitamin D3-induced apoptosis of retinoblastoma cells is associated with reciprocal changes of Bcl-2 and bax.

Experimental eye research, 2003, Volume: 77, Issue:1

The active vitamin D metabolite 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) and related substances have previously been tested in tissue culture and animal models of retinoblastoma for their use as anti-tumor drugs. However, despite of the potential therapeutic value, the molecular mechanisms through which 1,25-(OH)(2)D(3) inhibits the growth of retinoblastoma cells are incompletely understood. To elucidate possible signalling pathways for the anti-proliferative action of vitamin D compounds in retinal tumor cells, we analyzed the effect of 1,25-(OH)(2)D(3) and its synthetic analogue KH1060 on the growth of human retinoblastoma-derived Y79 cells. Vitamin D receptor (VDR) mRNA was detected by reverse transcription PCR in Y79 cells and in tissue specimens of human retinoblastoma. VDR transcripts were confirmed at the protein level by strong immunostaining of solid retinal tumors for VDR. Incubation with 1,25-(OH)(2)D(3) and KH1060 (10(-10)-10(-6)moll(-1)) decreased the number of Y79 cells in a timely and dose-dependent manner. Treatment with 1,25-(OH)(2)D(3) (10(-10)moll(-1)) for 24 hr caused cell cycle arrest in the G0/1 phase. Apoptosis of Y79 cells in response to 1,25-(OH)(2)D(3) was demonstrated by the means of TdT-dUTP terminal nick-end labelling (TUNEL), annexin V staining, and detection of DNA fragmentation on agarose gels. 1,25-(OH)(2)D(3)-induced programmed death of Y79 cells was accompanied by a concentration-dependent increase in Bax protein and a reduction in Bcl-2 content. These findings suggest that 1,25-(OH)(2)D(3) inhibits the growth of retinoblastoma cells by causing cell cycle arrest and apoptosis. 1,25-(OH)(2)D(3)-induced programmed death of retinoblastoma cells appears to involve reciprocal changes in Bcl-2 and Bax proteins.

Topics: Analysis of Variance; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Calcitriol; Cell Cycle; Dose-Response Relationship, Drug; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Interphase; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Receptors, Calcitriol; Retinal Neoplasms; Retinoblastoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors

2003