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Fluoroquinolones upregulate insulin-like growth factor-binding protein 3, inhibit cell growth and insulin-like growth

Chih-Ling Chung1, Chun-Lin Chen2

  • 1Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, 80424, Taiwan.

European Journal of Pharmacology
|February 29, 2024
PubMed

Insights

Fluoroquinolones (FQs) boost insulin-like growth factor-binding protein 3 (IGFBP-3) production, inhibiting cancer cell growth via a p53-dependent pathway. This reveals a novel anti-cancer mechanism for FQs and related compounds.

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Fluoroquinolones (FQs) possess known antibiotic properties and emerging anti-proliferative effects on cancer cells.
  • The precise mechanisms underlying FQ anti-cancer activity and immunomodulatory responses remain largely unelucidated.
  • Insulin-like growth factor-binding protein 3 (IGFBP-3) is implicated in regulating cell proliferation and survival.

Purpose of the Study:

  • To investigate the biological impact of Fluoroquinolones (FQs) on insulin-like growth factor-binding protein 3 (IGFBP-3) production.
  • To elucidate the role of the p53 tumor suppressor protein in mediating FQ-induced IGFBP-3 production and anti-proliferative effects.
  • To explore the potential of FQs as anti-cancer agents through novel mechanisms.

Main Methods:

  • Treatment of cultured cells and mouse models with FQs.
  • Quantification of IGFBP-3 mRNA expression and protein secretion.
  • Assessment of cell proliferation, apoptosis, and tumor growth in p53-dependent and -independent contexts, including p53-null and knockdown models.
  • Utilized a syngeneic mouse hepatocellular carcinoma (HCC) model for in vivo validation with ciprofloxacin.

Main Results:

  • FQs significantly increased IGFBP-3 mRNA expression and protein secretion in cultured cells and mouse models.
  • FQ-induced IGFBP-3 inhibited cell growth by suppressing IGF-I signaling and via an IGF-independent pathway.
  • The anti-proliferative effects of FQs were dependent on p53; suppression was reversed in p53-null and knockdown cells.
  • Ciprofloxacin demonstrated tumor cell apoptosis induction and tumor growth attenuation in a mouse HCC model.

Conclusions:

  • FQs induce IGFBP-3 production in a p53-dependent manner, leading to inhibition of cell proliferation.
  • This study reveals a novel mechanism of action for FQs as anti-proliferative agents.
  • Findings suggest potential therapeutic applications for FQs or their derivatives in cancer treatment and prevention strategies.
Keywords:
FluoroquinoloneIGFBP-3Insulin-like growth factorTumorp53

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