Farrerol Induces Cancer Cell Death via ERK Activation in SKOV3 Cells and Attenuates TNF-α-Mediated Lipolysis

Int J Mol Sci. 2021 Aug 30;22(17):9400. doi: 10.3390/ijms22179400.

Abstract

Farrerol (FA) is a flavanone isolated from the Chinese herbal medicine "Man-shan-hong" (Rhododendron dauricum L.). In the present study, FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, and it induced G2/M cell cycle arrest and cell apoptosis. Cell cycle distribution analysis via flow cytometry showed that FA decreased G1 populations and increased G2/M populations in SKOV3 cells. Additionally, Western blotting confirmed an increase in the expression level of proteins involved in the cell cycle, e.g., CDK and cyclins. FA-induced apoptosis in SKOV3 cells was also investigated using a TUNEL assay, and increased expression levels of proapoptotic factors, including Caspase-3 and poly ADP ribose polymerase (PARP), through the Extracellular signal-regulated kinase (ERK)/MAPK pathway were investigated. Proinflammatory cytokines (e.g., IL-6, TNF-α, and IL-1) have been identified as a driver of the pathological mechanisms underlying involuntary weight loss and impaired physical function, i.e., cachexia, during cancer; in the present study, we showed that farrerol attenuates TNF-α-induced lipolysis and increases adipogenic differentiation in 3T3-L1 cells. Thus, farrerol could potentially be used as an anticancer agent or anticachetic drug.

Keywords: adipogenesis; antitumor effect; cachexia; cell cycle arrest; farrerol; ovarian cancer.

MeSH terms

  • Apoptosis
  • Cell Cycle
  • Cell Proliferation
  • Chromones / pharmacology*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Lipolysis / drug effects*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Chromones
  • Tumor Necrosis Factor-alpha
  • farrerol
  • Extracellular Signal-Regulated MAP Kinases