Korean J Gynecol Oncol.  2007 Sep;18(3):165-171.

Treatment with sodium butyrate and rapamycin inhibit growth of human cervical cancer cells

Affiliations
  • 1Department of Obstetrics and Gynecology, School of Medicine, Keimyung University, Daegu, Korea. sdcha@dsmc.or.kr

Abstract


OBJECTIVE
To evaluate whether mTOR inhibition by rapamycin can enhance the inhibitory effect of sodium butyrate, a histone deacetylase (HDAC) inhibitor on human cervical cancer cell line HeLa.
METHODS
Cervical cancer cells (HeLa) were treated with sodium butyrate alone or in combination with rapamycin. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) assay and flow cytometry was performed to ascertain the effects of sodium butyrate and combinations of sodium butyrate with rapamycin. Expression of cell cycle related proteins were evaluated by Western blot analysis.
RESULTS
As proven previously rapamycin, the mTOR inhibitor was effective in reducing the cell growth of cervical cancer cell line HeLa. Rapamycin and sodium butyrate induced growth inhibition in a dose dependent manner, with 100 nM/L rapamycin and 10 mM/L sodium butyrate blocked 78% cell growth. FACS analysis data substantiated the competence of rapamycin in inducing G1 arrest of mammalian cells, and this ability was greatly enhanced by the combination of sodium butyrate and rapamycin. The percentage of sub G1 fraction of cells was remarkably increased by the combination of sodium butyrate and rapamycin. Sodium butyrate in combination with rapamycin showed the increased expression of CDK inhibitors p21, p27, and dephosphorylation of Rb whereas the expression levels of cyclin A, cyclin D1 and cyclin B1 were reduced.
CONCLUSION
The findings implicate that rapamycin could enhance the anti-cancer effect of sodium butyrate. Further in depth studies and in vitro studies would throw more light on the growth inhibitory mechanism and its potential use as therapeutic drugs of butyric acid and rapamycin.

Keyword

HeLa cell; Rapamycin; Sodium butyrate; Apotosis

MeSH Terms

Blotting, Western
Butyric Acid*
Cell Cycle
Cell Line
Cell Survival
Cyclin A
Cyclin B1
Cyclin D1
Flow Cytometry
HeLa Cells
Histone Deacetylases
Humans*
Mental Competency
Sirolimus*
Sodium*
Uterine Cervical Neoplasms*
Butyric Acid
Cyclin A
Cyclin B1
Cyclin D1
Histone Deacetylases
Sirolimus
Sodium
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