Macrocalyxin A inhibits proliferation and induces apoptosis of t (8;21) leukemia cells through mitochondrial signaling pathways and regulates AML-ETO mRNA expression

Mol Med Rep. 2015 Sep;12(3):3537-3542. doi: 10.3892/mmr.2015.3855. Epub 2015 May 27.

Abstract

Progress in the last decade has improved the treatment of acute myeloid leukemia (AML); however, the treatment of AML is also demanding and better treatments are required. The present study aimed to examine the antiproliferative and proapoptotic effects of macrocalyxin A (MA), a novel deterpenid compound, on AML cells. It was identified that MA significantly inhibits kasumi‑1 cell proliferation in a time‑ and dose‑dependent manner. Furthermore, low concentrations of MA were able to induce kasumi‑1 cell differentiation; however, high concentrations of MA induced kasumi‑1 cell apoptosis. MA was also able to increase the expression of mitochondrial membrane protein in a dose‑dependent manner while the ∆Ψm was reduced. Additionally, Bad expression in kasumi‑1 cells was increased when treated with MA, indicating that the intrinsic apoptotic pathway may be important in MA‑induced kasumi‑1 cell apoptosis, where the mitochondrial permeability transition pore is opened and the ΔΨm is reduced. In addition, it was demonstrated that AML‑ETO mRNA may also be important in MA‑induced apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Diterpenes / pharmacology*
  • Gene Expression Regulation, Leukemic / drug effects*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Oncogene Proteins, Fusion / genetics
  • RNA, Messenger / genetics
  • RUNX1 Translocation Partner 1 Protein
  • Signal Transduction / drug effects

Substances

  • AML1-ETO fusion protein, human
  • Antineoplastic Agents
  • Core Binding Factor Alpha 2 Subunit
  • Diterpenes
  • Oncogene Proteins, Fusion
  • RNA, Messenger
  • RUNX1 Translocation Partner 1 Protein
  • macrocalyxin A