Abstract:
UNLABELLED:Abstract Purpose: Sensitizing cancer cells to irradiation is a major challenge in clinical oncology. We aimed to define the signal transduction pathways involved in poly(ADP-ribose) polymerase (PARP) inhibitor-induced radiosensitization in various mammalian cancer lines. MATERIALS AND METHODS:Clonogenic survival assays and Western blot examinations were performed following telecobalt irradiation of cancer cells in the presence or absence of various combinations of PARP- and selective mitogen-activated protein kinase (MAPK) inhibitors. RESULTS:HO3089 resulted in significant cytotoxicity when combined with irradiation. In human U251 glioblastoma and A549 lung cancer cell lines, Erk1/2 and JNK/SAPK were found to mediate this effect of HO3089 since inhibitors of these kinases ameliorated it. In murine 4T1 breast cancer cell line, p38 MAPK rather than Erk1/2 or JNK/SAPK was identified as the main mediator of HO3089's radiosensitizing effect. Besides the aforementioned changes in kinase signaling, we detected increased p53, unchanged Bax and decreased Bcl-2 expression in the A549 cell line. CONCLUSIONS:HO3089 sensitizes cancer cells to photon irradiation via proapoptotic processes where p53 plays a crucial role. Activation of MAPK pathways is regarded the consequence of irradiation-induced DNA damage, thus their inhibition can counteract the radiosenzitizing effect of the PARP inhibitor.
journal_name
Int J Radiat Bioljournal_title
International journal of radiation biologyauthors
Hocsak E,Cseh A,Szabo A,Bellyei S,Pozsgai E,Kalai T,Hideg K,Sumegi B,Boronkai Adoi
10.3109/09553002.2014.934927subject
Has Abstractpub_date
2014-12-01 00:00:00pages
1152-61issue
12eissn
0955-3002issn
1362-3095journal_volume
90pub_type
杂志文章abstract:PURPOSE:It is considered that exposure to static magnetic fields (SMF) may have both detrimental and therapeutic effect, but the mechanism of SMF influence on the living organisms is not well understood. Since the adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) are involved in both physiological and...
journal_title:International journal of radiation biology
pub_type: 杂志文章
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journal_title:International journal of radiation biology
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journal_title:International journal of radiation biology
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abstract:PURPOSE:Ifosfamide as a chemotherapeutic drug is used for the treatment of different cancer types. The purpose of this study is the preparation of 99mTc-ifosfamide complex to be evaluated as a potential candidate for tumor imaging. MATERIALS AND METHODS:The radiolabeling of ifosfamide with technetium-99m was carried o...
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abstract::Only a small percentage of the DNA damage set by ionizing radiation in the living cell manifests itself as lethal. It is now increasingly accepted that clustered lesions may constitute the kind of damage that the repair enzymes cannot adequately deal with. The question is raised as to whether damage amplification reac...
journal_title:International journal of radiation biology
pub_type: 杂志文章
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journal_title:International journal of radiation biology
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pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:International journal of radiation biology
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journal_title:International journal of radiation biology
pub_type: 杂志文章
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journal_title:International journal of radiation biology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:International journal of radiation biology
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