Abstract
Abstract
Introduction/Objective
Hepatocellular carcinoma (HCC) is the most common cause of cancer-deaths worldwide. Garlic (Allium Sativum), is a natural-medicinal herb which has anti-fungal, anti-bacterial, anti-inflammatory, anti-virus, and antiproliferative activities. Garlic-oil soluble-sulfur-compounds, diallyl-thiosulphate, (DT) are more effective than water-soluble-compounds in protection against cancer due to its capacity to induce apoptosis and revise anti- multidrug-resistance. Histone deacetylases inhibitors (HDACIs) are inhibitors of anti-cancer agents that play a role in inducing death, differentiation, apoptosis induction, and cell-cycle arrest in different cancer-types. The present studying aims to investigate the anti-proliferative effect of organosulfur-oil DT extract of garlic by possible modulation of HDACIs role on HCC cell-lines.
Methods/Case Report
Two HDACIs, suberanilohydroxamic acid (SAHA) and trichostatinA (TSA), were used to investigate their role on proliferation of two HCC cell-lines, HepG2 and Hep3B, respectively. Cell proliferation was examined by Wst-1 assay, apoptosis induction signaling pathways, cell-cycle analysis, and western-blot analysis of the major oncogenic signaling pathways in the two tested cell-lines.
Results (if a Case Study enter NA)
Our data showed that DT significantly inhibited the cell-proliferation and induced cell-cycle arrest at G2/M phase in both HCC cell-lines. In addition, co-treatment of DT and HDACIs for 48h enhanced the cell inhibitory effect and induced apoptosis by up-regulation of p53, p21, and Bax protein expression and down- regulation of Bcl-2 and cyclin-D1 protein expression compared to control or each treatment alone. Furthermore, the data showed that DT significantly increased caspases-3 activity in Hep-G2 cell-line than that of Hep3B cell-line in a dose dependent-time compared to the control. Apoptosis induction was consistent with up-regulated caspase-3 activity, and HepG2 cells, but not Hep3B cells, showed a significant increase in response to co-treatment of DT with SAHA compared to co-treatment with TSA.
Conclusion
The data of the present study demonstrated that DT, non-toxicity compound, might be a new modulator for HDACIs effects, which in turn might be a promising prospective agent for HCC treatment.