Abstract

Background: Apiole was isolated from the leaves of various plants and vegetables and has been demonstrated to inhibit human colon cancer cell (COLO 205 cells) growth through induction of G0/G1 cell cycle arrest and apoptotic cell death. This study further explored the antitumor effects of apiole derivatives AP-02, 04, and 05 in COLO 205 cancer cells. Methods: Human breast (MDA-MB-231, ZR75), lung (A549, PE089), colon (COLO 205, HT 29), and hepatocellular (Hep G2, Hep 3B) cancer cells were treated with apiole and its derivatives in a dose-dependent manner. Flow cytometry analysis was subsequently performed to determine the mechanism of AP-02-induced G0/G1 cell cycle arrest. The in vivo antitumor effect of AP-02 (1 and 5 mg/kg, administered twice per week) was examined by treating athymic nude mice bearing COLO 205 tumor xenografts. The molecular mechanisms of AP-02-induced antitumor effects were determined using western blot analysis. Results: AP-02 was the most effective compound, especially for inhibition of COLO 205 colon cancer cell growth. The cytotoxicity of AP-02 in normal colon epithelial (FHC) cells was significantly lower than that in other normal cells derived from the breast, lung or liver. Flow cytometry analysis indicated that AP-02-induced G0/G1 cell cycle arrest in COLO 205 cells but not in HT 29 cells (< 5 μM for 24 h,∗∗p < 0.01). Tumor growth volume was also significantly inhibited in AP-02 (> 1 mg/kg)-treated athymic nude mice bearing COLO 205 tumor xenografts compared to control mice (∗p < 0.05). Furthermore, G0/G1 phase regulatory proteins (p53 and p21/Cip1) and an invasion suppressor protein (E-cadherin) were significantly upregulated, while cyclin D1 was significantly downregulated, in AP-02-treated tumor tissues compared to the control group (> 1 mg/kg,∗p < 0.05). Conclusions: Our results provide in vitro and in vivo molecular evidence of AP-02-induced anti-proliferative effects on colon cancer, indicating that this compound might have potential clinical applications.

Original languageEnglish
Article number188
JournalBMC Complementary and Alternative Medicine
Volume19
Issue number1
DOIs
Publication statusPublished - Jul 27 2019

Keywords

  • Antitumor
  • Apiole
  • COLO 205
  • G0/G1 arrest
  • Petroselinum crispum
  • Antineoplastic Agents/administration & dosage
  • Humans
  • Apoptosis/drug effects
  • Petroselinum/chemistry
  • Tumor Suppressor Protein p53/genetics
  • Dioxoles/administration & dosage
  • Xenograft Model Antitumor Assays
  • Cyclin D1/genetics
  • Animals
  • Mice, Nude
  • G1 Phase Cell Cycle Checkpoints/drug effects
  • Female
  • Mice
  • Resting Phase, Cell Cycle/drug effects
  • Colonic Neoplasms/drug therapy

ASJC Scopus subject areas

  • Complementary and alternative medicine

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