Aqueous extract of clove inhibits tumor growth by inducing autophagy through AMPK/ULK pathway

Phytother Res. 2019 Jul;33(7):1794-1804. doi: 10.1002/ptr.6367. Epub 2019 Apr 16.

Abstract

Cloves (Syzygium aromaticum), a traditional Chinese medicinal herb, displays broad biological activity. In the present study, the aqueous extract of clove (AEC) was prepared, and its anticancer affects were studied. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra-zolium (MTS) analysis revealed that AEC was able to inhibit cancer cell growth in vitro on several cancer cell lines; the IC50 is around 150 μg/ml for human pancreatic ASPC-1 and human colon HT-29 cancer cells. Treatment of the cancer cells with AEC also diminished the colony formation significantly in both human pancreatic ASPC-1 cancer cells and human colon HT-29 cancer cells. In vivo study revealed that AEC inhibited the tumor growth significantly in HT-29 xenograft mice model. Transmission electron microscope, flow cytometry assay, and fluorescence microscope analysis confirmed that AEC is capable of inducing cell autophagy. Further study showed that AMPK/ULK pathway plays an important role in AEC-induced autophagy in cancer cells. Analysis of AEC components was performed by liquid chromatograph mass spectrometer approach, and more than nine constitutes were identified in AEC fraction. The study provides evidence that AEC has potential to be developed as a novel anticancer agent or as an adjuvant in cancer chemotherapy.

Keywords: AMPK; anticancer; aqueous extract of clove; autophagy; traditional Chinese medicine.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Autophagy / drug effects
  • Cell Line, Tumor
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Plant Extracts / therapeutic use*
  • Protein-Serine-Threonine Kinases / metabolism
  • Syzygium*

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Protein-Serine-Threonine Kinases