Abstract:
:The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent with high tumor-selective cytotoxicity. The congenital and acquired resistance of some cancer types including malignant melanoma and osteosarcoma impede the current TRAIL therapy of these cancers. Since fine tuning of the intracellular Ca2+ level is essential for cell function and survival, Ca2+ dynamics could be a promising target for cancer treatment. Recently, we demonstrated that mitochondrial Ca2+ removal increased TRAIL efficacy toward malignant melanoma and osteosarcoma cells. Here we report that mitochondrial Ca2+ overload leads to tumor-selective sensitization to TRAIL cytotoxicity. Treatment with the mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157 and oxidative phosphorylation inhibitor antimycin A and FCCP resulted in a rapid and persistent mitochondrial Ca2+ rise. These agents also increased TRAIL sensitivity in a tumor-selective manner with a switching from apoptosis to a nonapoptotic cell death. Moreover, we found that mitochondrial Ca2+ overload led to increased mitochondrial fragmentation, while mitochondrial Ca2+ removal resulted in mitochondrial hyperfusion. Regardless of their reciprocal actions on the mitochondrial dynamics, both interventions commonly exacerbated TRAIL-induced mitochondrial network abnormalities. These results expand our previous study and suggest that an appropriate level of mitochondrial Ca2+ is essential for maintaining the mitochondrial dynamics and the survival of these cells. Thus, disturbing mitochondrial Ca2+ homeostasis may serve as a promising approach to overcome the TRAIL resistance of these cancers with minimally compromising the tumor-selectivity.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Ohshima Y,Takata N,Suzuki-Karasaki M,Yoshida Y,Tokuhashi Y,Suzuki-Karasaki Ydoi
10.3892/ijo.2017.4096subject
Has Abstractpub_date
2017-10-01 00:00:00pages
1146-1158issue
4eissn
1019-6439issn
1791-2423journal_volume
51pub_type
杂志文章abstract::The effect of immune cells on the growth and development of human prostatic cancer cells was investigated. Cell proliferation of androgen-independent human prostatic cancer cells JCA-1 was reduced 30-40% with the supplementation of a growth modulating activity present in lymphocyte conditioned medium. The slower growi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.4.979
更新日期:1994-10-01 00:00:00
abstract::The hematogenous metastasis of cancer consists of a multistep process. It is surmised that a number of interactions between cancer and endothelial cells occur, with cell adhesion molecules playing certain roles in this process. The authors conducted an investigation on the interaction between human cancer cells and cu...
journal_title:International journal of oncology
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abstract::WNT signaling pathway is implicated in carcinogenesis and embryogenesis. We have previously cloned and characterized WNT10A, and demonstrated up-regulation of WNT10A in gastric cancer. Here, we investigated expression of WNT10A mRNA in various types of human cancer. WNT10A mRNA was detected in 10 out of 12 esophageal ...
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journal_title:International journal of oncology
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journal_title:International journal of oncology
pub_type: 杂志文章
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更新日期:2007-04-01 00:00:00
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更新日期:2001-11-01 00:00:00
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journal_title:International journal of oncology
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doi:
更新日期:2003-08-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-03-01 00:00:00
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journal_title:International journal of oncology
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更新日期:2008-01-01 00:00:00
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journal_title:International journal of oncology
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doi:
更新日期:2006-02-01 00:00:00
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journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
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更新日期:1999-10-01 00:00:00
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doi:10.3892/ijo.17.6.1151
更新日期:2000-12-01 00:00:00
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journal_title:International journal of oncology
pub_type: 杂志文章,评审
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journal_title:International journal of oncology
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journal_title:International journal of oncology
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