Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo

Molecules. 2020 Oct 10;25(20):4608. doi: 10.3390/molecules25204608.


Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.

Keywords: Cedrus atlantica extract (CAt extract); apoptosis; cell cycle; hepatocellular carcinoma (HCC).

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cedrus / chemistry*
  • Cell Cycle / drug effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Female
  • Flow Cytometry
  • Gas Chromatography-Mass Spectrometry
  • Hep G2 Cells
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / metabolism
  • Plant Extracts / chemistry*
  • Plant Extracts / therapeutic use*
  • Proto-Oncogene Proteins c-akt / metabolism


  • Plant Extracts
  • Proto-Oncogene Proteins c-akt