Issue
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.
HSP90 inhibitor enhances anti-proliferative and apoptotic effects of celecoxib on HT-29 colorectal cancer cells via increasing BAX/BCL-2 ratio
Corresponding Author(s) : M. Saravani
moh.saravani@gmail.com
Cellular and Molecular Biology,
Vol. 62 No. 12: Issue 12
Abstract
Due to the high prevalence and mortality rate of colorectal cancer (CRC), new treatment approaches like combination therapy seem to be necessary. The relationship between chronic inflammation and colorectal cancer development and progression has been shown to be important. Celecoxib, a selective COX-2 inhibitor, is the only non-steroidal anti-inflammatory drug (NSAID) that has been approved for cancer therapy and prevention. Because of cardiovascular side effects of COX-2 inhibitors, combination therapy may improve the therapeutic profile. 17-Demethoxy-17-allylamino geldanamycin (17-AAG), a heat shock protein 90 (HSP90) inhibitor, shows anti-inflammatory effects via down-regulation of the key mediators of inflammation such as Nuclear Factor κB (NF-kB), JAK/Signal Transducer and Activator of Transcription (JAK/STAT). Thus, we studied the effect(s) of combination of 17-AAG and celecoxib on HT-29 cells viability and apoptosis induction. Based on MTT results, we showed an increase in the inhibitory effect of celecoxib when combined with 17-AAG, especially at low a concentration of celecoxib. Flow cytometry analysis demonstrated that apoptosis induction is probably the mechanism of additive inhibitory effects of 17-AAG and celecoxib combination. To explore the possible mechanism of apoptosis induction by 17-AAG and celecoxib combination, levels of BAX and BCL-2 proteins were determined by western blotting. The BAX/BCL-2 ratio in the combination group was increased compared to 17-AAG or celecoxib alone, mainly via decreasing BCL-2 levels. In conclusion, 17-AAG, increased inhibitory effects of celecoxib on HT-29 cells, probably by induction of apoptosis.
Keywords
HSP90
celecoxib
colorectal cancer
apoptosis
BAX
BCL-2.
Mohammadi, A., Yaghoobi, M. M., GholamhoseynianNajar, A., Kalantari-Khandani, B., Sharifi, H., & Saravani, M. (2016). HSP90 inhibitor enhances anti-proliferative and apoptotic effects of celecoxib on HT-29 colorectal cancer cells via increasing BAX/BCL-2 ratio. Cellular and Molecular Biology, 62(12), 62–67. https://doi.org/10.14715/cmb/2016.62.12.11
Download Citation
Endnote/Zotero/Mendeley (RIS)BibTeX