Towards Novel Anti-tumor Strategies for Hepatic Cancer: epsilon-Viniferin in Combination with Vincristine Displays Pharmacodynamic Synergy at Lower Doses in HepG2 Cells

Creative Commons License

ÖZDEMİR F., AKALIN ÇİFTÇİ G., Sen M., Onder N. I., Iscan A., KUTLU H. M., ...More

OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY, no.5, pp.324-334, 2014 (SCI-Expanded) identifier identifier identifier


Hepatocellular carcinoma is the fifth most common cancer and the third leading cause of cancer-related deaths worldwide. The efficacy of novel combination treatments are increasingly evaluated with use of integrative biology research and development (R&D) strategies and methodological triangulation. We investigated the anti-tumor effect of -viniferin alone, and the putative synergy of -viniferin with vincristine on the growth of HepG2 cells in vitro. Growth inhibition and apoptosis induction were determined by MTT assay and annexin V/propidium iodide (PI), respectively. Morphological changes and DNA fragmentation were investigated under electron microscopy and by agarose gel electrophoresis, respectively. The results collectively showed that treating cells with -viniferin and vincristine significantly inhibited cell viability at lower doses as compared to each agent applied alone. IC50 values for -viniferin and vincristine were determined as 98.3 and 52.5M at 24h, respectively. IC50 value of -viniferin in combination with vincristine was 15.8+11.25M (mean/SD) at 24h. The viability of cells treated with 17.9M vincristine alone for 24h was 79.62%; it reduced to 26.53% when 25M -viniferin was added in combination with vincristine (p<0.05). We found that combination of drugs promoted the sensitivity of cells against to vincristine treatment. The effect of combined use was in support of a synergistic pharmacodynamic effect. Moreover, low doses of the combination regimen induced phosphatidyl re-localization, morphological changes, and DNA fragmentation, and therefore caused apoptotic death. This study thus suggests that low concentrations of -viniferin and vincristine can enhance the anti-tumor effects efficiently by inducing HepG2 cell apoptosis. Further studies in other model systems are warranted with a view to potential future applications in the clinic of such combination regimens and their putative mechanism of action in the observed synergy reported here.