Study of the antitumor mechanisms of apiole derivatives (AP-02) from Petroselinum crispum through induction of G0/G1 phase cell cycle arrest in human COLO 205 cancer cells

Kuan Hsun Wu, Wen Jui Lee, Tzu Chun Cheng, Hui Wen Chang, Li Ching Chen, Chia Chang Chen, Hsiu Man Lien, Teng Nan Lin, Yuan Soon Ho

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1 Citation (Scopus)

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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