1'-Acetoxychavicol acetate-induced cytotoxicity is accompanied by a rapid and drastic modulation of glutathione metabolism.

The effect of 1'-acetoxychavicol acetate (ACA), an anticarcinogenic compound naturally obtained from rhizomes and seeds of South East Asia plants, on the intracellular concentration of glutathione and the activities of enzymes related to glutathione metabolism was studied in Ehrlich ascites tumor cells. We showed in a previous study that ACA induced apoptosis in tumor cells and the cell death was reversed by the addition of N-acetlycysteine or glutathione ethylester. Here we found that ACA caused a rapid decrease in glutathione level in less than 10 min after ACA exposure. At the time, glutathione reductase activity was significantly inhibited and gamma-glutamyl cysteine increased by ACA exposure. These results show that ACA caused the decrease in the intracellular GSH levels in Ehrlich ascites tumor cells, suggesting that ACA-induced decrease of the cellular GSH levels can lead to growth arrest of cancer and enhancement of the efficacy other anticancer drugs.

Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways.

Adenosine, a modulator of neuronal function in the mammalian central nervous system, exerts a neuroprotective effect via the adenosine A(1) receptor; however, its effect on neural stem cells (NSCs) remains unclear. Because adenosine is released in response to pathological conditions and NSCs play a key role in neuroregeneration, we tested the hypothesis that adenosine is capable of stimulating NSC proliferation. We demonstrated that NSCs dominantly express adenosine A(1) and A(2B) receptors. Adenosine and the adenosine A(1) receptor agonist cyclopentyladenosine (CPA) increased proliferation of NSCs, and this CPA-induced cell proliferation was attenuated by the A(1) antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPA). CPA also induced phosphorylation of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase/ERK kinase (MEK), and Akt, and their phosphorylation was inhibited by DPCPA. In addition, CPA-induced cell proliferation was inhibited by MEK and Akt inhibitors. These results suggest that activation of adenosine A(1) receptor-stimulated proliferation of NSCs occurs via MEK/ERK and Akt signaling pathways.