Abstract 3211: Citral is the major component of ginger-derived terpenes to mediate p53-dependent apoptosis in cancer cells

Steam distillation of ginger yields a mixture of twenty two terpenes. This mixture has anti-proliferative effect on over fifteen different human and mouse cancer cell lines tested in our previous studies. Since the mixture is heterogeneous, it cannot be developed into a therapeutic drug. Hence, we tested individual terpenes from the ginger extract to identify its bioactive component(s). Camphene and alpha-pinene together constitute 10% of the ginger terpene extract and have no effect on cancer cell proliferation. On the other hand, citral a mixture of the two isomers, neral and geranial which constitute 30-50% of the ginger terpene extract, inhibits proliferation of ECC-1, OVCAR-3, OVCAR5, OVCAR 433 with IC50 between 20-50 μM. The decrease in proliferation of the cells is due to induction of apoptosis by citral as measured by monitoring Annexin V and propidium iodide staining and expression of cleaved caspase3. Treatment of cancer cells with citral results in a rapid increase in intracellular Reactive Oxygen Species (ROS). The cellular stress resulting from ROS generation leads to phosphorylation of the Ser-15 residue of p53. Activation of p53 via this phosphorylation event leads to apoptosis in cancer cells. When cells are pre-treated with ROS inhibitor, N-acetyl cysteine (NAC), citral induced apoptosis is inhibited. Similarly inhibition of p53 by pifithrin-α or knockdown of the tumor suppressor by siRNA attenuates the pro-apoptotic response of citral. There is a significa...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Cancer Chemistry Source Type: research