Induction of Intrinsic and Extrinsic Apoptosis Pathways in the Human Leukemic MOLT-4 Cell Line by Terpinen-4-ol

Abstract

Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). Inthis study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in thehuman leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristicmorphological features of apoptosis by Wright’s staining. The mode of cell death was confirmed to be apoptosisby flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNAhistograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through anintrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome cinto the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activationresulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated themitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity alsoincreased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic andextrinsic pathways.