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  3. 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

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

  • BMC Complement Altern Med. 2019 Jul 27;19(1):188. doi: 10.1186/s12906-019-2590-9.
Kuan-Hsun Wu 1 2 3,  Wen-Jui Lee 4,  Tzu-Chun Cheng 5,  Hui-Wen Chang 6,  Li-Ching Chen 7 8 9,  Chia-Chang Chen 10,  Hsiu-Man Lien 11,  Teng-Nan Lin 12,  Yuan-Soon Ho 13 14 15
Affiliations

Affiliations

  • 1 The Ph.D. Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan.
  • 2 Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 3 Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
  • 4 Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University and National Health Research Institutes, Taipei, Taiwan.
  • 5 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, 110, Taiwan, Republic of China.
  • 6 Department of Medical Laboratory, and Cancer Research Center of Taipei Medical University Hospital, Taipei, Taiwan.
  • 7 Division of Breast Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan.
  • 8 Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
  • 9 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.
  • 10 School of Management, Feng Chia University, Taichung, Taiwan.
  • 11 Research Institute of Biotechnology, Hungkuang University, No.1018, Sec. 6, Taiwan Blvd., Shalu Dist, Taichung City, 43302, Taiwan. lien736@gmail.com.
  • 12 Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. bmltn@ibms.sinica.edu.tw.
  • 13 School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, 110, Taiwan, Republic of China. hoyuansn@tmu.edu.tw.
  • 14 Department of Medical Laboratory, and Cancer Research Center of Taipei Medical University Hospital, Taipei, Taiwan. hoyuansn@tmu.edu.tw.
  • 15 TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan. hoyuansn@tmu.edu.tw.
PMID: 31351461 DOI: 10.1186/s12906-019-2590-9
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.

Keywords

Antitumor; Apiole; COLO 205; G0/G1 arrest; Petroselinum crispum.

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