The synergistic antitumor effects of all-trans retinoic acid and C-phycocyanin on the lung cancer A549 cells in vitro and in vivo

Eur J Pharmacol. 2015 Feb 15:749:107-14. doi: 10.1016/j.ejphar.2015.01.009. Epub 2015 Jan 21.

Abstract

The anticancer effects and mechanism of all-trans retinoic acid (ATRA), C-phycocyanin (C-PC) or ATRA+C-PC on the growth of A549 cells were studied in in vitro and in vivo experiments. The effects of C-PC and ATRA on the growth of A549 cells were determined. The expression of CDK-4 and caspase-3, and the cellular apoptosis levels were detected. The tumor model was established by subcutaneous injection of A549 cells to the left axilla of the NU/NU mice. The weights of tumor and the spleen were tested. The viabilities of T-cells and spleen cells, TNF levels, the expression of Bcl-2 protein and Cyclin D1 gene were examined. Results showed both C-PC and ATRA could inhibit the growth of tumor cells in vivo and in vitro. ATRA+C-PC cooperatively showed a higher antitumor activity. The dosage of ATRA was reduced when it was administered with C-PC together, and the toxicity was reduced as well. ATRA+C-PC could decrease CDK-4 but increase caspase-3 protein expression level and induce cell apoptosis. ATRA alone could lower the activities of T lymphocytes and spleen weights, but the combination with C-PC could effectively promote viability of T cells and spleen. C-PC+ATRA could up-regulate TNF, and down-regulate Bcl-2 and Cyclin D1 gene. The combination might inhibit tumor growth by inhibiting the progress of cell cycle, inducing cell apoptosis and enhancing the body immunity.

Keywords: A-549 cancer cells; All-trans retinoic acid; Apoptosis; C-phycocyanin; Cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin D1 / genetics
  • Cyclin-Dependent Kinase 4 / genetics
  • Drug Synergism
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice, Nude
  • Phycocyanin* / administration & dosage
  • Phycocyanin* / pharmacology
  • Phycocyanin* / therapeutic use
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Spleen / drug effects
  • T-Lymphocytes / drug effects
  • Tretinoin* / administration & dosage
  • Tretinoin* / pharmacology
  • Tretinoin* / therapeutic use
  • Tumor Burden / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antineoplastic Agents
  • Ccnd1 protein, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • Phycocyanin
  • Bcl2 protein, mouse
  • Cyclin D1
  • Tretinoin
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Caspase 3