Combinatorial effect of blueberry extracts and oxaliplatin in human colon cancer cells

J Cell Physiol. 2019 Aug;234(10):17242-17253. doi: 10.1002/jcp.28341. Epub 2019 Feb 19.

Abstract

The use of natural compounds to potentiate the effect of drugs and lower their adverse effects is an active area of research. The objective is to determine the effect of combined blueberry extracts (BE) and oxaliplatin (OX) in colon cancer cells. The results demonstrated that treatments of BE/OX showed inhibitory effects on HCT-116 cell and nontoxic effect on CCD-18Co normal colon cells. Flow cytometry analysis indicated that treatment with the BE, OX or in combination could induce G0/G1 cell cycle arrest, apoptosis, increase of reactive oxygen species, and induce loss of mitochondrial membrane potential in HCT-116 cells. Furthermore, after treatments, the expression of inflammatory cytokines was decreased, cyclin D1 and CDK4 were decreased; caspases-3 and 9 were activated; the Akt/Bad/Bcl-2 pathway was modulated. Moreover, the combination treatment had a considerably higher growth inhibitory effect on human colon cancer HCT-116 cells than that of BE or oxaliplatin alone. Our results showed that BE increased the anticolon cancer effect of OX making it an attractive strategy as adjuvant therapy to potentially reduce the adverse side effects associated with chemotherapeutic drugs.

Keywords: apoptosis; blueberry extracts; cell cycle; colon cancer; oxaliplatin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blueberry Plants / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Membrane Potential, Mitochondrial / drug effects*
  • Oxaliplatin / pharmacology*
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Plant Extracts
  • Reactive Oxygen Species
  • Oxaliplatin