A Dihydrobenzofuran Lignan Induces Cell Death by Modulating Mitochondrial Pathway and G2/M Cell Cycle Arrest

A dihydrobenzofuran lignan, the dimerization product of caffeic acid methyl ester, has shown pronounced antileishmanial and antiplasmodial activities. The present study showed the effect of this compound on cell cycle and apoptosis. Flow cytometric analysis revealed that the cells were arrested in t...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2009-05, Vol.52 (10), p.3184-3190
Main Authors: Bose, Julie S, Gangan, Vijay, Prakash, Ravi, Jain, Swatantra Kumar, Manna, Sunil Kumar
Format: Article
Language:English
Subjects:
Antimalarials
Antineoplastic Agents
Antiprotozoal Agents
Apoptosis - drug effects
Apoptosis Regulatory Proteins - drug effects
Benzofurans - pharmacology
Biological and medical sciences
Caffeic Acids
Caspase 3 - metabolism
Cell Cycle - drug effects
G2 Phase
General aspects
Humans
Jurkat Cells
Lignans - pharmacology
Medical sciences
Mitochondria - drug effects
Mitochondria - metabolism
Pharmacology. Drug treatments
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Summary:A dihydrobenzofuran lignan, the dimerization product of caffeic acid methyl ester, has shown pronounced antileishmanial and antiplasmodial activities. The present study showed the effect of this compound on cell cycle and apoptosis. Flow cytometric analysis revealed that the cells were arrested in the G2/M phase. Activation of caspase 3, but not caspase 8, generation of ROS, upstream of caspase-3, release of cytochrome c,increase in Bax level, and decrease in Bcl-2 level suggested the involvement of mitochondrial damage. Loss of mitochondrial transmembrane potential independent of caspase activation further suggested the mode of apoptosis. Dihydrobenzofuran-mediated cell death was absent in Bcl-xL-overexpressed cells. Overall, our results justify the role of dihydrobenzofuran lignan as potential antitumor agent, causing G2/M arrest and apoptosis involving the mitochondrial controlled pathway. These findings open promising insights as to how this specific dihydrobenzofuran lignan mediates cytotoxicity and may prove a molecular rationale for future therapeutic interventions in carcinogenesis.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm8015766