β-Carotene Induces Apoptosis in Human Esophageal Squamous Cell Carcinoma Cell Lines via the Cav-1/AKT/NF-κB Signaling Pathway

J Biochem Mol Toxicol. 2016 Mar;30(3):148-57. doi: 10.1002/jbt.21773. Epub 2016 Jan 6.

Abstract

β-carotene, a type of terpenoid, has many metabolic and physiological functions. In particular, β-carotene has an antitumor effect. However, the efficacy of β-carotene against esophageal squamous cell carcinoma (ESCC) remains unclear. In our study, β-carotene inhibited the growth of ESCC cells and downregulated expression of the Caveolin-1 (Cav-1) protein. Cav-1 protein was expressed only in ESCC cells, not in Het-1A cells. Moreover, β-carotene triggered apoptosis, induced cell cycle G0⁄G1 phase arrest, and inhibited cell migration. To explore the mechanism involved in these processes, we further examined the effect of β-carotene on the Cav-1-mediated AKT/NF-κB pathway. The results showed that the level of AKT and NF-κB phosphorylation was dramatically inhibited, which led to an increase in the Bax/Bcl-2 ratio. Correspondingly, the activity of Caspase-3 was also enhanced. These data suggest that β-carotene has an antiproliferative role in ESCC cells and may be a promising chemotherapeutic agent for use against ESCC cells.

Keywords: AKT/NF-κB; Apoptosis; Caveolin-1; Esophageal Squamous Cell Carcinoma; Proliferation; β-Carotene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Caveolin 1 / metabolism*
  • Cell Line, Tumor
  • Esophageal Neoplasms / enzymology
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology*
  • Humans
  • NF-kappa B / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • beta Carotene / pharmacology*

Substances

  • CAV1 protein, human
  • Caveolin 1
  • NF-kappa B
  • beta Carotene
  • Proto-Oncogene Proteins c-akt