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Nutrition and Disease

The Production of Reactive Oxygen Species and the Mitochondrial Membrane Potential Are Modulated during Onion Oil–Induced Cell Cycle Arrest and Apoptosis in A549 Cells

Xin-jiang Wu^*,1, Thorsten Stahl, Ying Hu, Fekadu Kassie^** and Volker Mersch-Sundermann^*

^* Institute of Indoor and Environmental Toxicology, Faculty of Medicine, Justus-Liebig-University of Giessen, Aulweg 123, D-35385 Giessen, Germany; Interdisciplinary Research Center, Heinrich-Buff-Ring 26-32, Justus-Liebig University, D-35392 Giessen, Germany; and ^** The Cancer Center, University of Minnesota, Minneapolis, MN 55455

¹ To whom correspondence should be addressed. Email: toxwu{at}yahoo.com.hk.

Protective effects of Allium vegetables against cancers have been shown extensively in experimental animals and epidemiologic studies. We investigated cell proliferation and the induction of apoptosis by onion oil extracted from Allium cepa, a widely consumed Allium vegetable, in human lung cancer A549 cells. GC/MS analysis suggested that propyl sulfides but not allyl sulfides are major sulfur-containing constituents of onion oil. Onion oil at 12.5 mg/L significantly induced apoptosis (13% increase of apoptotic cells) as indicated by sub-G1 DNA content. It also caused cell cycle arrest at the G2/M phase; 25 mg/L onion oil increased the percentage of G2/M cells almost 6-fold compared with the dimethyl sulfoxide control. The action of onion oil may occur via a reactive oxygen species–dependent pathway because cell cycle arrest and apoptosis were blocked by the antioxidants N-acetylcysteine and exogenous glutathione. Marked collapse of the mitochondrial membrane potential suggested that dysfunction of the mitochondria may be involved in the oxidative burst and apoptosis induced by onion oil. Expression of phospho-cdc2 and phospho-cyclin B1 were downregulated by onion oil, perhaps accounting for the G2/M arrest. Overall, these results suggest that onion oil may exert chemopreventive action by inducing cell cycle arrest and apoptosis in tumor cells.

KEY WORDS: • onion • allium • cell cycle • apoptosis • chemoprevention