Naphthylchalcones induce apoptosis and caspase activation in a leukemia cell line: The relationship between mitochondrial damage, oxidative stress, and cell death

Bioorg Med Chem. 2010 Nov 15;18(22):8026-34. doi: 10.1016/j.bmc.2010.09.025. Epub 2010 Sep 16.

Abstract

In this study, we investigated the effects of 24 chalcone derivatives from 2-naphthylacetophenone toward a lymphoblastic leukemia cell line (L1210). Three compounds, called R7, R13, and R15, presented concentration- and time-dependent cytotoxicity and induced cellular death by apoptosis via mitochondrial injury and oxidative stress. The effects of these compounds appear to occur through different mechanisms because R13 and R7 induced a greater disturbance of mitochondrial potential, and all compounds induced disturbances of cellular ATP content and increased caspase-3 activity before cellular death. These compounds also interfered with antioxidant enzymes activities and GSH content through different mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Agents / toxicity
  • Apoptosis*
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Chalcone / analogs & derivatives*
  • Chalcone / therapeutic use
  • Chalcone / toxicity
  • Chalcones / chemistry*
  • Chalcones / therapeutic use
  • Chalcones / toxicity
  • Humans
  • Leukemia / drug therapy*
  • Mitochondria / drug effects*
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism

Substances

  • Antineoplastic Agents
  • Chalcones
  • Reactive Oxygen Species
  • Chalcone
  • Caspase 3