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Proteasome inhibitor-I Enhances Tunicamycin-Induced Chemosensitization of Prostate Cancer Cells Through Regulation of NF-κB and CHOP Expression

Proteasome inhibitor-I Enhances Tunicamycin-Induced Chemosensitization of Prostate Cancer Cells Through Regulation of NF-κB and CHOP Expression

Pham Thi Thu Huong, Dong-Oh Moon, Sun Ok Kim, Kyoon Eon Kim, Sook Jung Jeong, Ki Won Lee, Kyung Sang Lee, Jae Hyuk Jang, Raymond Leo Erikson, Jong Seog Ahn, Bo Yeon Kim

Cell Signal. 2011 May;23(5):857-65.

PMID: 21276850

Abstract:

Although endoplasmic reticulum (ER) stress induction by some anticancer drugs can lead to apoptotic death of cancer cells, combination therapy with other chemicals would be much more efficient. It has been reported that proteasome inhibitors could induce cancer cell death through ER-stress. Our study, however, showed a differential mechanism of proteasome inhibitor-I (Pro-I)-induced cell death. Pro-I significantly enhanced apoptotic death of PC3 prostate cancer cells pretreated with tunicamycin (TM) while other signaling inhibitors against p38, mitogen activated kinase (MEK) and phosphatidyl-inositol 3-kinase (PI3K) did not, as evidenced by cell proliferation and cell cycle analyses. NF-κB inhibition by Pro-I, without direct effect on ER-stress, was found to be responsible for the TM-induced chemosensitization of PC3 cells. Moreover, TM-induced/enhancer-binding protein (C/EBP) homologous protein (CHOP) expression was enhanced by Pro-I without change in GRP78 expression. CHOP knockdown by siRNA also showed a significant decrease in Pro-I chemosensitization. All these data suggest that although TM could induce both NF-κB activation and CHOP expression through ER-stress, both NF-κB inhibition and increased CHOP level by Pro-I are required for enhanced chemosensitization of PC3 prostate cancer cells. Thus, our study might contribute to the identification of anticancer targets against prostate cancer cells.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42410915	Proteasome Inhibitor I			Price

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