title: A dihydrobenzofuran lignan induces cell death by modulating mitochondrial pathway and G2/M cell cycle arrest.
abstract: 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.
authors.affiliation: Reliance Life Sciences Pvt. Ltd., Mumbai, India.
authors.forename: Julie S
authors.initials: JS
authors.lastname: Bose
authors.forename: Vijay
authors.initials: V
authors.lastname: Gangan
authors.forename: Ravi
authors.initials: R
authors.lastname: Prakash
authors.forename: Swatantra Kumar
authors.initials: SK
authors.lastname: Jain
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Manna
mesh_terms: D000962:Antimalarials; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D002109:Caffeic Acids; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D016195:G2 Phase; D006801:Humans; D019169:Jurkat Cells; D017705:Lignans / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000962:Antimalarials; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D051017:Apoptosis Regulatory Proteins; D001572:Benzofurans; D002109:Caffeic Acids; D017705:Lignans; D053148:Caspase 3; C497945:caffeic acid methyl ester