Luteolin induces cell cycle arrest and apoptosis through extrinsic and intrinsic signaling pathways in MCF-7 breast cancer cells

J Environ Pathol Toxicol Oncol. 2014;33(3):219-31. doi: 10.1615/jenvironpatholtoxicoloncol.2014010923.

Abstract

Luteolin is a common flavonoid that exists in medicinal herbs, fruits, and vegetables. Luteolin has biochemical functions including anti-allergy, anti-inflammation, and anti-cancer functions. However, its efficacy and precise mode of action against breast cancer are still under study. To elucidate whether luteolin exhibits an anticancer effect in breast cancer, MCF-7 breast cancer cells were incubated with luteolin, and apoptosis was assessed by observing nuclear morphological changes and by performing cell viability assay, cell cycle analysis, annexin V-FITC/PI double staining, western blotting, RT-PCR, and mitochondrial membrane potential measurements. Luteolin inhibited growth through perturbation of cell cycle progression at the sub-G1 and G1 phases in MCF-7 cells. Furthermore, luteolin enhanced the expression of death receptors, such as DR5, and activated caspase cascades. It enhanced the activities of caspase-8/-9/-3 in a dose-dependent manner, followed by inactivation of PARP. Activation of caspase-8 and caspase-9 induced caspase-3 activity, respectively, in apoptosis of extrinsic and intrinsic pathways. Luteolin also induced mitochondrial membrane potential collapse and cytochrome c release, and increased Bax expression by inhibiting expression of Bcl-2. Taken together, these results suggest that luteolin provokes cell cycle arrest and induces apoptosis by activating the extrinsic and intrinsic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexins / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Cycle Checkpoints / drug effects*
  • Cell Nucleus / drug effects
  • Cell Survival / drug effects
  • Female
  • Fluorescein-5-isothiocyanate / chemistry
  • Humans
  • Luteolin / pharmacology*
  • MCF-7 Cells
  • Membrane Potential, Mitochondrial
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*

Substances

  • Annexins
  • Antineoplastic Agents
  • Fluorescein-5-isothiocyanate
  • Luteolin