Arborinine suppresses ovarian cancer development through inhibition of LSD1

Life Sci. 2022 Feb 15:291:120275. doi: 10.1016/j.lfs.2021.120275. Epub 2021 Dec 31.

Abstract

Aims: Epithelial ovarian carcinoma is the most lethal female reproductive malignancy in the world. Paclitaxel and carboplatin are generally the first-line treatment drugs for ovarian cancer patients, but numerous patients may develop chemotherapy resistance. Thus, it is urgent to identify novel drugs for ovarian cancer treatment. Arborinine has been known as a broad-spectrum anti-tumor agent due to it possesses a potent cytotoxic effect on various cancer cells.

Materials and methods: This study aimed to evaluate its anti-tumor effect and the potential underlying mechanism on ovarian cancer cell line SKOV3. The effect of arborinine on SKOV3 cell proliferation and movement were evaluated by MTT assay and cell migration and invasion assays, respectively. The RT-qPCR and Western Blot assays were employed to determine target gene expression. The tumor-bearing mouse model was applied to assess the anti-tumor effect of arborinine in vivo.

Key findings: Our results demonstrated that arborinine treatment significantly inhibited the cell proliferation and tumor growth of SKOV3 in a dose-dependent manner. Arborinine treatment dose-dependently reduced LSD1 expression, resulting in increased H3K4m1 expression. Importantly, arborinine also potently suppressed cell migration and invasion of SKOV3 via reducing epithelial-mesenchymal transition (EMT) of SKOV3.

Significance: Arborinine may serve as a potential drug candidate for developing new strategies for ovarian cancer treatment.

Keywords: Arborinine; EMT; LSD1; Ovarian cancer; SKOV3.

MeSH terms

  • Acridines / metabolism
  • Acridines / pharmacology*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • China
  • Cisplatin / pharmacology
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Histone Demethylases / drug effects
  • Histone Demethylases / metabolism*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness / pathology
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / pathology
  • Ovary / metabolism
  • Paclitaxel / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Acridines
  • Antineoplastic Agents
  • arborinine
  • Histone Demethylases
  • KDM1A protein, human
  • Paclitaxel
  • Cisplatin