NDLI: Disruption of microtubules sensitizes the DNA damage-induced apoptosis through inhibiting nuclear factor κB (NF-κB) DNA-binding activity.

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Disruption of microtubules sensitizes the DNA damage-induced apoptosis through inhibiting nuclear factor κB (NF-κB) DNA-binding activity.

Content Provider	Europe PMC
Author	Lee, Hyunji Jeon, Juhee Ryu, Young Sue Jeong, Jae Eun Shin, Sanghee Zhang, Tiejun Kang, Seong Wook Hong, Jang Hee Hur, Gang Min
Copyright Year	2010
Abstract	The massive reorganization of microtubule network involves in transcriptional regulation of several genes by controlling transcriptional factor, nuclear factor-kappa B (NF-κB) activity. The exact molecular mechanism by which microtubule rearrangement leads to NF-κB activation largely remains to be identified. However microtubule disrupting agents may possibly act in synergy or antagonism against apoptotic cell death in response to conventional chemotherapy targeting DNA damage such as adriamycin or comptothecin in cancer cells. Interestingly pretreatment of microtubule disrupting agents (colchicine, vinblastine and nocodazole) was observed to lead to paradoxical suppression of DNA damage-induced NF-κB binding activity, even though these could enhance NF-κB signaling in the absence of other stimuli. Moreover this suppressed NF-κB binding activity subsequently resulted in synergic apoptotic response, as evident by the combination with Adr and low doses of microtubule disrupting agents was able to potentiate the cytotoxic action through caspase-dependent pathway. Taken together, these results suggested that inhibition of microtubule network chemosensitizes the cancer cells to die by apoptosis through suppressing NF-κB DNA binding activity. Therefore, our study provided a possible anti-cancer mechanism of microtubule disrupting agent to overcome resistance against to chemotherapy such as DNA damaging agent.
ISSN	10118934
Volume Number	25
PubMed Central reference number	PMC2966993
Issue Number	11
PubMed reference number	21060745
Journal	Journal of Korean Medical Science [J. Korean Med. Sci]
e-ISSN	15986357
DOI	10.3346/jkms.2010.25.11.1574
Language	English
Publisher	The Korean Academy of Medical Sciences
Publisher Date	2010-10-26
Access Restriction	Open
Rights License	This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2010 The Korean Academy of Medical Sciences.
Subject Keyword	NF-kappa B Apoptosis DNA Damage Microtubules Signaling
Content Type	Text
Resource Type	Article
Subject	Medicine

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