Open AccessDepletion of Neuroguidin/CANu1 sensitizes human osteosarcoma U2OS cells to doxorubicin
Author(s) -
Jin Hee Park,
Choong Ryoul Sihn,
Yeon Su Lee,
Sung Jae Lee,
Sang Hoon Kim
Publication year - 2011
Publication title -
bmb reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.511
H-Index - 77
eISSN - 1976-670X
pISSN - 1976-6696
DOI - 10.5483/bmbrep.2011.44.1.46
Subject(s) - doxorubicin , osteosarcoma , gene knockdown , nucleolus , apoptosis , cancer research , small hairpin rna , viability assay , chemistry , microbiology and biotechnology , cytotoxicity , cell , cancer cell , population , biology , medicine , chemotherapy , cancer , in vitro , nucleus , biochemistry , genetics , environmental health
Osteosarcoma is a primary bone cancer which occurs mainly in children. Neuroguidin/CANu1 is a nucleolar protein involved in the maintenance of ribosomal structure. In this study, we investigated the effect of Neuroguidin/CANu1 depletion on the response of osteosarcoma cells to doxorubicin. In normal circumstances, Neuroguidin/CANu1 is localized at nucleoli, which translocates to nuclear foci in the presence of doxorubicin. shRNA knockdown of Neuroguidin/CANu1 did not affect cell viability in the absence of doxorubicin, but led to enhanced cytotoxicity in doxorubicin-treated cells. Doxorubicin increased the population of apoptotic cells by 3-fold in Neuroguidin/CANu1-depleted cells compared to that in control cells. Depletion of Neuroguidin/CANu1 mRNA induced the expression of p21 and the cleavage of PARP, leading to increased caspase-3/7 activity. Together, these results suggest that Neuroguidin/CANu1 is required for maintaining cellular homeostasis and may contribute to the improved efficiency of chemotherapy.