17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry

17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry

Aim: Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific cha...

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Бібліографічні деталі
Дата:2012
Автори: Chaklader, M., Das, P., Pereira, J.A., Law, A., Chattopadhyay, S., Chatterjee, R., Mondal, A., Law, S.
Формат: Стаття
Мова:English
Опубліковано: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2012
Назва видання:Experimental Oncology
Теми:
Original contributions
Онлайн доступ:http://dspace.nbuv.gov.ua/handle/123456789/138688
Теги: Додати тег
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Цитувати:17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry / M. Chaklader, P. Das, J.A. Pereira, A. Law, S. Chattopadhyay, R. Chatterjee, A. Mondal, S. Law // Experimental Oncology. — 2012. — Т. 34, № 2. — С. 90-96. — Бібліогр.: 24 назв. — англ.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
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spelling irk-123456789-1386882018-06-20T03:05:58Z 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry Chaklader, M. Das, P. Pereira, J.A. Law, A. Chattopadhyay, S. Chatterjee, R. Mondal, A. Law, S. Original contributions Aim: Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. Methods: We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. Results: Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery — heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. Conclusion: Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned. 2012 Article 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry / M. Chaklader, P. Das, J.A. Pereira, A. Law, S. Chattopadhyay, R. Chatterjee, A. Mondal, S. Law // Experimental Oncology. — 2012. — Т. 34, № 2. — С. 90-96. — Бібліогр.: 24 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/138688 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Original contributions
Original contributions
spellingShingle Original contributions
Original contributions
Chaklader, M.
Das, P.
Pereira, J.A.
Law, A.
Chattopadhyay, S.
Chatterjee, R.
Mondal, A.
Law, S.
17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry
Experimental Oncology
description Aim: Peritoneal or retro-peritoneal sarcomatosis related malignant ascites formation is a rare but serious consequence of the locoregional metastatic event. The present work aimed to study the effect of the Hsp90 inhibitor (17-AAG), an ansamycin analog, on cell cycle and DNA replication specific chaperone-clients interaction in the event of peritoneal sarcoma related malignant ascites formation in mouse model at the late stage of malignant growth. Methods: We administered 17-AAG, an Hsp90 inhibitor, divided doses (330 μg/kg b.w./day for first five days then next ten days with166 μg/kg b.w./day) through intra-peritoneal route of inbred Swiss albino mice bearing full grown peritoneal malignant ascites of sarcoma-180. Our study was evaluated by peripheral blood hemogram analysis, malignant ascitic cytology, cell viability test, survival time and mitotic indexing. Furthermore, flowcytometric HSP90, TERT, CyclinD1, PCNA and GM-CSF expression analysis has been considered for special objective of the study. Results: Our experimental efforts reduced the aggressive proliferation of malignant ascites by drastic downregulation of TERT and cyclin D1 on the verge of cell cycle entry along with DNA replication processivity factor PCNA by directly modulating their folding machinery — heat shock protein 90. Consequently, we observed that malignant ascitic cells became error prone during the event of karyokinesis and produced micronucleus containing malignant cells with low viability. Peripheral neutrophilia due to over-expression of GM-CSF by the peritoneal malignant ascites were also controlled by the treatment with 17-AAG and overall, the treatment modality improved the median survival time. Conclusion: Finally we can conclude that 17AAG administration might serve as a prospective pharmacological agent for the management of peritoneal sarcoma related malignant ascites and throws light towards prolonged survival of the patients concerned.
format Article
author Chaklader, M.
Das, P.
Pereira, J.A.
Law, A.
Chattopadhyay, S.
Chatterjee, R.
Mondal, A.
Law, S.
author_facet Chaklader, M.
Das, P.
Pereira, J.A.
Law, A.
Chattopadhyay, S.
Chatterjee, R.
Mondal, A.
Law, S.
author_sort Chaklader, M.
title 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry
title_short 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry
title_full 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry
title_fullStr 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry
title_full_unstemmed 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry
title_sort 17-aag mediates targeting of hsp90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin d1 during cell cycle entry
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2012
topic_facet Original contributions
url http://dspace.nbuv.gov.ua/handle/123456789/138688
citation_txt 17-AAG mediates targeting of HSP90 limits tert activity in peritoneal sarcoma related malignant ascites by downregulating cyclin D1 during cell cycle entry / M. Chaklader, P. Das, J.A. Pereira, A. Law, S. Chattopadhyay, R. Chatterjee, A. Mondal, S. Law // Experimental Oncology. — 2012. — Т. 34, № 2. — С. 90-96. — Бібліогр.: 24 назв. — англ.
series Experimental Oncology
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first_indexed 2023-10-18T21:19:15Z
last_indexed 2023-10-18T21:19:15Z
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