Daucus carota Pentane-Based Fractions Suppress Proliferation and Induce Apoptosis in Human Colon Adenocarcinoma HT-29 Cells by Inhibiting the MAPK and PI3K Pathways

J Med Food. 2015 Jul;18(7):745-52. doi: 10.1089/jmf.2014.3225. Epub 2015 Jan 19.

Abstract

Daucus carota L. ssp. carota (Apiacea, wild carrot, Queen Anne's lace) has been used in folk medicine throughout the world and recently was shown to possess anticancer and antioxidant activities. This study aims to determine the anticancer activity of the pentane fraction (F1) and the 1:1 pentane:diethyl ether fraction (F2) of the Daucus Carota oil extract (DCOE) against human colon adenocarcinoma cell lines (HT-29 and Caco-2). Treatment of cells with various concentrations of F1 or F2 fractions produced a dose-dependent inhibition of cell proliferation. Flow cytometric analysis indicated that both fractions induced sub-G1 phase accumulation and increased apoptotic cell death. Western blot revealed the activation of caspase-3, PARP cleavage, and a considerable increase in Bax and p53 levels, and a decrease in Bcl-2 level. Treatment of HT-29 cells with either fraction markedly decreased the levels of both phosphorylated Erk and Akt. Furthermore, the combined treatment of F1 or F2 with wortmannin showed no added inhibition of cell survival suggesting an effect of F1 or F2 through the phosphatidyl inositol 3-kinase (PI3K) pathway. This study proposes that DCOE fractions (F1 and F2) inhibit cell proliferation by inducing cell cycle arrest and apoptosis in HT-29 cells through the suppression of mitogen-activated protein kinase (MAPK)/Erk and PI3K/Akt pathways.

Keywords: Daucus carota; MAPK; PI3K; apoptosis; colon cancer; proliferation.

MeSH terms

  • Adenocarcinoma / pathology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Caco-2 Cells
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology*
  • Daucus carota / chemistry*
  • Extracellular Signal-Regulated MAP Kinases / analysis
  • G1 Phase / drug effects
  • HT29 Cells
  • Humans
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Pentanes / pharmacology*
  • Phosphoinositide-3 Kinase Inhibitors*
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Proto-Oncogene Proteins c-akt / analysis

Substances

  • Antineoplastic Agents, Phytogenic
  • Pentanes
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Extracts
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinases