8-Cetylberberine inhibits growth of lung cancer in vitro and in vivo

Life Sci. 2018 Jan 1;192:259-269. doi: 10.1016/j.lfs.2017.11.012. Epub 2017 Nov 11.


Aims: This study is aimed at detecting the anti-tumor efficacy of a new berberine (BBR) derivative 8-cetylberberine (HBBR), which has a significant improvement in hydrophobicity and pharmacological effects compared to BBR.

Main methods: The human non-small lung cancer cell line A549 and normal human lung epithelial cells (MRC-5) were cultured to observe inhibition in vitro. Cell viability was analyzed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of HBBR on cell cycle arrest and apoptosis were assessed by flow cytometry and western blotting. In animal studies, BALB/c nude mice were subcutaneously injected with A549 cells in the armpit and administrated with different dose of HBBR and BBR. The body weight, organ coefficient and tumor inhibitory rate were recorded to evaluate the effect of HBBR in vivo.

Key findings: The data showed that HBBR induced G1-phase cycle arrest by interfering with the expression of Cyclins D1 and Cyclin E1, increased apoptosis by inducing caspase pathway, and probably inhibited the PI3K/Akt pathway in A549 cells. In addition, animal experiments proved that oral administration of HBBR at a dose of 10mg/kg could significantly inhibit tumor growth, which is stronger than the 120mg/kg dose of BBR treatment.

Significance: Our results suggest that HBBR showed a significantly higher anti-tumor efficacy than BBR in vitro and in vivo and could be a potential therapy for lung cancers.

Keywords: Anti-tumor; Apoptosis; Berberine derivative; Cell cycle arrest; Lung cancer.

MeSH terms

  • A549 Cells
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Apoptosis / drug effects
  • Berberine / analogs & derivatives*
  • Berberine / pharmacology
  • Berberine / therapeutic use
  • Biomarkers, Tumor / blood
  • Body Weight / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival
  • Cyclin D1 / biosynthesis
  • Cyclin D1 / genetics
  • Dose-Response Relationship, Drug
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Signal Transduction / drug effects
  • Tumor Burden
  • Xenograft Model Antitumor Assays


  • 8-cetylberberine
  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • Berberine
  • Cyclin D1