Isoliensinine, a Bioactive Alkaloid Derived from Embryos of Nelumbo nucifera, Induces Hepatocellular Carcinoma Cell Apoptosis through Suppression of NF-κB Signaling

J Agric Food Chem. 2015 Oct 14;63(40):8793-803. doi: 10.1021/acs.jafc.5b02993. Epub 2015 Oct 1.

Abstract

Isoliensinine (isolie) is an alkaloid produced by the edible plant Nelumbo nucifera. Here, we unveiled that isolie was able to provoke HepG2, Huh-7, and H22 hepatocellular carcinoma (HCC) cell apoptosis. Isolie decreased NF-κB activity and constitutive phosphorylation of NF-κB p65 subunit at Ser536 in HCC cells. Overexpression of p65 Ser536 phosphorylation mimics abrogated isolie-mediated HCC cell apoptosis. Furthermore, intraperitoneal injection of isolie inhibited the growth of Huh-7 xenografts in nude mice. Additionally, isolie given by both intraperitoneal injection and gavage diminished the proliferation of transplanted H22 cells in Kunming mice. Reduced tumor growth in vivo was associated with inhibited p65 phosphorylation at Ser536 and declined NF-κB activity in tumor tissues. Finally, we revealed that isolie was bioavailable in the blood of mice and exhibited no detectable toxic effects on tumor-bearing mice. Our data provided strong evidence for the anti-HCC effect of isolie.

Keywords: NF-κB; Nelumbo nucifera; apoptosis; hepatocellular carcinoma; isoliensinine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / administration & dosage
  • Alkaloids / chemistry
  • Animals
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / physiopathology
  • Cell Line, Tumor
  • Humans
  • Isoquinolines / administration & dosage*
  • Isoquinolines / chemistry
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / physiopathology
  • Male
  • Mice
  • Mice, Nude
  • Molecular Structure
  • NF-kappa B / metabolism*
  • Nelumbo / chemistry*
  • Nelumbo / embryology
  • Plant Extracts / administration & dosage*
  • Plant Extracts / chemistry
  • Signal Transduction / drug effects*

Substances

  • Alkaloids
  • Isoquinolines
  • NF-kappa B
  • Plant Extracts
  • isoliensinine