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Plos One : Depletion of Hdac6 Enhances Cisplatin-induced Dna Damage and Apoptosis in Non-small Cell Lung Cancer Cells, Volume 7

By Schneider, Guenter

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Book Id: WPLBN0003935949
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Depletion of Hdac6 Enhances Cisplatin-induced Dna Damage and Apoptosis in Non-small Cell Lung Cancer Cells, Volume 7  
Author: Schneider, Guenter
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection (Contemporary)
Historic
Publication Date:
Publisher: Plos

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Schneider, G. (n.d.). Plos One : Depletion of Hdac6 Enhances Cisplatin-induced Dna Damage and Apoptosis in Non-small Cell Lung Cancer Cells, Volume 7. Retrieved from http://worldlibrary.in/


Description
Description : Histone deacetylase inhibitors (HDACi) are promising therapeutic agents which are currently used in combination with chemotherapeutic agents in clinical trials for cancer treatment including non-small cell lung cancer (NSCLC). However, the mechanisms underlying their anti-tumor activities remain elusive. Previous studies showed that inhibition of HDAC6 induces DNA damage and sensitizes transformed cells to anti-tumor agents such as etoposide and doxorubicin. Here, we showed that depletion of HDAC6 in two NSCLC cell lines, H292 and A549, sensitized cells to cisplatin, one of the first-line chemotherapeutic agents used to treat NSCLC. We suggested that depletion of HDAC6 increased cisplatin-induced cytotoxicity was due to the enhancement of apoptosis via activating ATR/Chk1 pathway. Furthermore, we showed that HDAC6 protein levels were positively correlated with cisplatin IC50 in 15 NSCLC cell lines. Lastly, depletion of HDAC6 in H292 xenografts rendered decreased tumor weight and volume and exhibited increased basal apoptosis compared with the controls in a xenograft mouse model. In summary, our findings suggest that HDAC6 is positively associated with cisplatin resistance in NSCLC and reveal HDAC6 as a potential novel therapeutic target for platinum refractory NSCLC.

 

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