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Oncol Rep. 2017 Aug;38(2):859-865. doi: 10.3892/or.2017.5750. Epub 2017 Jun 23.

BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells.

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Tumor Targeted Therapy and Translational Medicine Laboratory, Basic College of Medicine, Jilin Medical University, Jilin, Jilin 132013, P.R. China.
Department of Histology and Embryology, Basic College of Medicine, Jilin Medical University, Jilin, Jilin 132013, P.R. China.
Physical Examination Center, Jilin Integrated Traditional Chinese and Western Medicine Hospital, Jilin, Jilin 132013, P.R. China.


The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p‑p53‑Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer.

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