Dichamanetin inhibits cancer cell growth by affecting ROS-related signaling components through mitochondrial-mediated apoptosis

Anticancer Res. 2013 Dec;33(12):5349-55.

Abstract

Background/aim: Dichamanetin is a C-benzylated flavanone isolated as a major secondary metabolite from Piper sarmentosum, a plant used as a spice in Southeast Asia. This study aimed to investigate the path through which dichamanetin exerts its antiproliferative effect.

Materials and methods: The study of several signaling cellular components, namely, reactive oxygen species (ROS) levels, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) transcription factor, mitochondrial membrane potential, DNA binding, poly ADP-ribose polymerase (PARP1) inhibition and proteasome inhibition was performed using an enzyme-linked immunosorbent (ELISA) assay, cell sorting, and western blot.

Results: Dichamanetin significantly reduced the cell viability of various types of human cancer cells (HT-29 colon, DU145 prostate, and MDA-MB-231 breast cancer) in a concentration- and time-dependent manner and induced G1 arrest of the cell cycle. It was also demonstrated that the selective cytotoxic effect of dichamanetin in cancer cells is mediated by the induction of oxidative stress.

Conclusion: Our findings suggest that dichamanetin isolated from an edible herb has cancer chemotherapeutic potential.

Keywords: DNA binding; NF-κB inhibition; PARP-1; Piper sarmentosum; Piperaceae; ROS; cytotoxicity; dichamanetin; mitochondrial membrane potential.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / drug effects*
  • Blotting, Western
  • Cell Division / drug effects*
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Flavanones / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / physiology*
  • NF-kappa B / metabolism
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects*

Substances

  • Flavanones
  • NF-kappa B
  • Reactive Oxygen Species
  • dichamanetin