Isoferulic acid inhibits human leukemia cell growth through induction of G2/M‑phase arrest and inhibition of Akt/mTOR signaling

Mol Med Rep. 2020 Mar;21(3):1035-1042. doi: 10.3892/mmr.2020.10926. Epub 2020 Jan 9.


Hematologic malignancy is a serious disease that develops quickly and aggressively, severely threatening human health owing to its high mortality. The current study aimed to evaluate the antitumor effects of isoferulic acid (IFA) on leukemia cells and investigate the possible molecular mechanisms. Hematologic cancer cell lines (Raji, K562 and Jurkat) were treated with IFA in a dose‑dependent manner and proliferation was measured by a cell proliferation assay. Cell cycle arrest was detected via flow cytometry using propidium iodide (PI) staining. Cell apoptosis and apoptosis‑associated signal pathways were analyzed via Annexin V/PI staining and western blot assays, respectively. IFA inhibited cell viability, induced cell apoptosis and triggered cell cycle arrest in G2/M phase in Raji, K562, and Jurkat cells in a dose‑dependent manner. In response to IFA treatment, the levels of cleaved poly(ADP‑ribose) polymerase and cleaved caspase‑3 were increased in Jurkat and K562 cells, which was associated with increased phosphorylation of Cdc2 and reduction of Cyclin B1 levels. IFA remarkably attenuated the phosphorylation of mTOR and Akt in Jurkat cells. Collectively, the present data suggested that IFA had therapeutic effects on Jurkat, K562, and Raji cells, indicating it as a promising candidate for the treatment of hematologic malignancy.

Keywords: isoferulic acid; hematologic malignancy; apoptosis; cell cycle arrest; akt/mTor signaling.

MeSH terms

  • Cinnamates / pharmacology*
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Leukemia* / drug therapy
  • Leukemia* / metabolism
  • Leukemia* / pathology
  • M Phase Cell Cycle Checkpoints
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • TOR Serine-Threonine Kinases / metabolism*


  • Cinnamates
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • isoferulic acid