Coenzyme Q-10 reduced the aberrant production of extracellular matrix proteins in uterine leiomyomas through transforming growth factor beta 3

F S Sci. 2024 Nov;5(4):342-351. doi: 10.1016/j.xfss.2024.07.004. Epub 2024 Jul 14.

Abstract

Objective: To evaluate the impact of coenzyme Q-10 (CoQ-10) on the dysregulated synthesis of extracellular matrix proteins mediated by transforming growth factor beta 3 (TGF-β3) in uterine leiomyomas.

Design: Laboratory study.

Setting: University.

Patients: None.

Interventions: Treatment of immortalized uterine myometrial and leiomyoma cells to TGF-β3 and CoQ-10.

Main outcome measures: The protein concentrations of collagen 1A1 (COL1A1), collagen 3A1 (COL3A1), collagen 11A1 (COL11A1), and fibronectin (FN1) were assessed through western blot analysis after treatment of immortalized uterine myometrial and leiomyoma cells with both transforming growth factor beta (TGF-β) 3 and concentrations of CoQ-10 at 10, 50, and 100 μM concurrently for 24 hours.

Results: Immortalized uterine leiomyoma and myometrial cells exposed to TGF-β3 for 24 hours demonstrated a significant up-regulation of COL1A1, COL3A1, COL11A1, and FN1 compared with untreated cells. In leiomyoma cells, concurrent treatment with CoQ-10 over the same timeframe revealed a dose-dependent decrease in these protein concentrations compared with those in cells treated with TGF-β3 alone. At the highest concentration of 100 μM of CoQ-10, significant decreases in the amounts of COL1A1 (0.59 ± 0.10-fold), COL3A1 (0.46 ± 0.09-fold), COL11A1 (0.53 ± 0.09-fold), and FN1 (0.56 ± 0.09-fold) were observed. Similarly, myometrial cells exposed to both TGF-β3 and CoQ-10 demonstrated a dose-responsive decline in the amount of extracellular matrix protein compared with cells exposed to TGF-β3 alone. Significant reductions in the amounts of COL1A1 (0.75 ± 0.03-fold), COL3A1 (0.48 ± 0.06-fold), COL11A1 (0.38 ± 0.06), and FN1 (0.69 ± 0.04-fold) were appreciated at 100-μM CoQ-10.

Conclusion: Coenzyme Q-10 mitigated the aberrant production of key biomarkers of the extracellular matrix mediated by TGF-β3 in uterine leiomyomas. Our findings highlight a promising nonhormonal compound that can counteract the fibroproliferative process inherent to leiomyomas.

Keywords: Leiomyoma; coenzyme Q-10; extracellular matrix; transforming growth factor beta 3.

MeSH terms

  • Cell Line, Tumor
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain / metabolism
  • Collagen Type III / genetics
  • Collagen Type III / metabolism
  • Extracellular Matrix Proteins* / genetics
  • Extracellular Matrix Proteins* / metabolism
  • Female
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Humans
  • Leiomyoma* / drug therapy
  • Leiomyoma* / metabolism
  • Leiomyoma* / pathology
  • Myometrium / drug effects
  • Myometrium / metabolism
  • Myometrium / pathology
  • Transforming Growth Factor beta3* / genetics
  • Transforming Growth Factor beta3* / metabolism
  • Ubiquinone* / analogs & derivatives
  • Ubiquinone* / pharmacology
  • Uterine Neoplasms* / drug therapy
  • Uterine Neoplasms* / metabolism
  • Uterine Neoplasms* / pathology

Substances

  • Ubiquinone
  • coenzyme Q10
  • Transforming Growth Factor beta3
  • Extracellular Matrix Proteins
  • Collagen Type III
  • Collagen Type I, alpha 1 Chain
  • Collagen Type I
  • COL3A1 protein, human
  • Fibronectins
  • COL1A1 protein, human
  • TGFB3 protein, human