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

Patompong Khaw-On,Ratana Banjerdpongchai

doi:10.7314/apjcp.2012.13.7.3073

Patompong Khaw-On, Ratana Banjerdpongchai

Open Access

https://doi.org/10.7314/apjcp.2012.13.7.3073

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Abstract

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

Highlights

Apoptosis is a process by which cells undergo organized self-destruction without an inflammatory response
Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol
Reduction of mitochondrial transmembrane potential apoptosis in MOLT-4 cells, the induction of apoptosis (ΔΨm) by terpinen-4-ol was examined for the morphology

Summary

Introduction

Apoptosis is a process by which cells undergo organized self-destruction without an inflammatory response. In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright’s staining.

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Conclusion