Agrimol B present in Agrimonia pilosa Ledeb impedes cell cycle progression of cancer cells through G0 state arrest

Biomed Pharmacother. 2021 Sep:141:111795. doi: 10.1016/j.biopha.2021.111795. Epub 2021 Jun 4.

Abstract

Cancer recurrence poses a significant challenge. At the cellular level, recurrence takes place as a result of reactivation of dormant cancer cells residing at G0 phase. The aim of the study was to identify compounds that can trap prostate and lung cancer cells in G0 phase from a new Chinese herb recipe, Astringent recipe, consisting of Radix Paeoniae Alba, Agrimonia pilosa Ledeb, Fructus Mume, Fritillaria thunbergii Miq., Ganoderma Lucidum Karst, and Astragalus membranaceus (Fisch.) Bunge. Astringent recipe impeded cell cycle progression in prostate and lung cancer cells by rounding them up at G0 phase by flow cytometric analysis of cancer cells stained with Hoechst 33342 and Pyronin Y, respectively, for DNA and RNA. The anti-cancer efficacy of the recipe was found to be attributable to Agrimonia pilosa Ledeb. Further study established that agrimol B, a polyphenol derived from Agrimonia pilosa Ledeb, contributed to the activity of the herb. The action of agrimol B on the cancer cells was likely derived from its effect on c-MYC, SKP2 and p27 by immunoblotting and immunofluorescence. Oral administration of Agrimonia pilosa Ledeb or agrimol B reduced growth of prostate cancer cell xenograft in animal. In conclusion, Agrimol B can enrich for prostate and lung cancer cells in G0 state and influence key regulators that govern G0 status.

Keywords: Agrimol B; Ellagic acid; Lung cancer; Polyphenols; Prostate cancer; Quiescent cancer cells.

MeSH terms

  • A549 Cells
  • Agrimonia*
  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Butanones / isolation & purification
  • Butanones / pharmacology*
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / physiology
  • Dose-Response Relationship, Drug
  • Ellagic Acid / pharmacology
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • G1 Phase Cell Cycle Checkpoints / physiology
  • HEK293 Cells
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Tumor Burden / drug effects*
  • Tumor Burden / physiology

Substances

  • Antineoplastic Agents, Phytogenic
  • Butanones
  • Phenols
  • Plant Extracts
  • Ellagic Acid
  • agrimol B