The HDAC inhibitor Vorinostat diminishes the in vitro metastatic behavior of Osteosarcoma cells

BioMed Research International
Xiaodong MuKurt R Weiss

Abstract

Osteosarcoma (OS) is the most common primary malignancy of bone and affects patients in the first two decades of life. The greatest determinant of survival is the presence of pulmonary metastatic disease. The role of epigenetic regulation in OS, specifically the biology of metastases, is unknown. Our previous study with the murine OS cell populations K7M2 and K12 demonstrated a significant correlation of metastatic potential with the DNA methylation level of tumor suppressor genes. In the current study, we investigated if the histone deacetylase (HDAC) inhibitor, vorinostat, could regulate the metastatic potential of highly metastatic OS cells. Our results revealed that vorinostat treatment of highly metastatic K7M2 OS cells was able to greatly reduce the proliferation and metastatic potential of the cells. Morphological features related to cell motility and invasion were changed by vorinostat treatment. In addition, the gene expressions of mTOR, ALDH1, and PGC-1 were downregulated by vorinostat treatment. These data suggest that vorinostat may be an effective modulator of OS cell metastatic potential and should be studied in preclinical models of metastatic OS.

References

Nov 2, 2001·Nature·T ReyaI L Weissman
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Jul 22, 2004·The Oncologist·Neyssa MarinaRichard Gorlick
Aug 15, 2006·Clinical Orthopaedics and Related Research·Kurt R WeissJohnny Huard
Jun 1, 2007·Molecular Oncology·Santiago Ropero, Manel Esteller
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Jun 14, 2013·Clinical Orthopaedics and Related Research·Xiaodong MuKurt Weiss
Oct 21, 2014·Journal of Cancer Therapy·Nicholas GrecoKurt R Weiss

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Citations

Jul 2, 2016·Stem Cells International·Ander AbarrategiRene Rodriguez
Mar 27, 2018·PloS One·Alejandro ParralesJoy M Fulbright
May 14, 2016·Oncotarget·Liu DingLi Zhihong
Jul 1, 2020·International Journal of Cancer. Journal International Du Cancer·Jeremy J McGuireConor C Lynch
Apr 20, 2021·Life Sciences·M Janaki RamaiahRajasekhar Reddy Manyam
Aug 21, 2021·Naunyn-Schmiedeberg's Archives of Pharmacology·Yasmine A HassanAsser I Ghoneim

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Methods Mentioned

BETA
Assay
PCR

Software Mentioned

RTCA

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