Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 12
Antiproliferative effects of retinoic acid and histone deacetylase inhibitor Bml-210 on
human cervical cancer HeLa cells
Veronika V. Borutinskaite1, 2, Ruta Navakauskiene 1 and Karl-Eric Magnusson2
1Department of Developmental Biology, Institute of Biochemistry, LT-08662 Vilnius,
Lithuania. E-mail: verbo@imk.liu.se ruta.navakauskiene@bchi.lt
2Division of Medical Microbiology, Department of Molecular and Clinical Medicine,
Linköping University, SE-581 85 Linköping, Sweden. E-mail: karma@imk.liu.se
Human papillomaviruses (HPVs) have been associated with a number of neoplastic lesions,
most notably cervical cancer which is one of the major forms of cancer world wide. Human
cervical carcinoma HeLa cells contain integrated human papillomavirus type 18 (HVP18).
Retinoic acid is a key regulator of epithelial cell differentiation and a growth inhibitor in vitro
of HeLa cervical carcinoma cells. Cellular responses to RA are mediated by nuclear retinoic
acid receptors (RARs) and retinoid X receptors (RXRs). On the other hand, histone
deacetylase inhibitors have been shown to be chemopreventive agents for the treatment of
cancer cells.
In this study, we have studied the antiproliferative effect of retinoic acid (RA) and histone
deacetylase inhibitor Bml-210 on HeLa cells, and particularly the effects on the protein
expression that may be involved in the cell cycle control and apoptosis. Our data suggest that
a combination of RA and Bml-210 leads to cell growth inhibition with following apoptosis in
a treatment time- dependent manner. We confirm that Bml-210 alone or in combination with
RA cause a marked increase in the level of p21, which coincides with the increased level of
transcription factor Sp1. The changes in p53 level are only under RA influence. We also
discovered that histone deacetylase inhibitor Bml-210 causes increased levels of antiapoptotic
protein Bcl-2 and phosphorylated p38 MAPK; these link in cell cycle arrest with
response to extracellular stimuli. Our results suggest that RA and Bml-210 are involved in
different signalling pathways that regulate cell cycle arrest and lead to apoptosis of HeLa
cells.
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