Solanum nigrum Suppress Angiogenesis-Mediated Tumor Growth Through Inhibition of the AKT/mTOR Pathway

Am J Chin Med. 2016;44(6):1273-1288. doi: 10.1142/S0192415X16500713. Epub 2016 Sep 15.

Abstract

Solanum nigrum L., an edible plant and local dish, has been assigned anticancer activities. However, the anticancer mechanisms of S. nigrum are poorly understood. Here, we investigated whether the water or polyphenol extracts of S. nigrum (SNWE or SNPE) could inhibit angiogenesis-mediated tumor growth. In nude mice bearing tumor xenografts, SNWE or SNPE significantly reduced the volume and weight of the tumors, and decreased the expression of CD31, a marker for angiogenesis. SNWE or SNPE was found to inhibit the VEGF-induced capillary structure formation of endothelial cells. The chicken egg chorioallantoic membrane (CAM) and matrigel plug assays showed further that SNWE or SNPE inhibited tumor angiogenesis. In human umbilical vascular endothelial cells (HUVECs), SNWE or SNPE suppressed the VEGF-induced activation of AKT and mTOR. Moreover, SNWE or SNPE inhibited the viability of human hepatoma HepG2 cells, and these effects were correlated with the extent of inhibition of the AKT/mTOR pathway. Taken together, our data imply that SNWE or SNPE downregulated the AKT/mTOR pathway in HUVECs and HepG2 cells, which lead to reduced tumor growth and angiogenesis.

Keywords: AKT/mTOR Pathway; Angiogenesis; Solanum nigrum L.; Tumor Growth.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinoma, Hepatocellular / blood supply
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / genetics*
  • Chick Embryo
  • Disease Models, Animal
  • Female
  • Hep G2 Cells
  • Heterografts
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / genetics*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics*
  • Phytotherapy*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / therapeutic use*
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / physiology*
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics*
  • Signal Transduction / physiology
  • Solanum nigrum / chemistry*
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / physiology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Proto-Oncogene Proteins c-akt