Effects of Cedrus atlantica extract on acute myeloid leukemia cell cycle distribution and apoptosis

Mol Biol Rep. 2020 Nov;47(11):8935-8947. doi: 10.1007/s11033-020-05947-w. Epub 2020 Nov 4.

Abstract

This study investigated the anti-leukemic effects of Cedrus atlantica extract (CAt extract) on cell cycle distribution and apoptosis in human acute myeloid leukemia (AML) cells. AML often occurs in older adults, accounting for 60% of the cases, and is likely to be resistant to chemotherapy due to multidrug resistance, resulting in early death during cancer treatment. With the increasing focus on prevention medicine, natural plant components are being used as a major source for the development of therapeutic drugs or functional foods to cure or alleviate the disease. Cedrus species are known to have anti-inflammatory, antimicrobial, antiviral, and anticancer effects; however, the anticancer effects of CAt extract have not been elucidated. In this study, CAt extract demonstrated an inhibitory effect on human leukemia cells in a concentration-dependent manner; CAt extract induced G0/G1 phase arrest via restrained protein levels of p-Rb and cell cycle-related proteins. After CAt extract exposure, the extrinsic and intrinsic apoptotic pathways were activated through caspase-8, -9, and -3 cleavage. Additionally, CAt extract suppressed VEGF, MMP-2, and MMP-9 expression. This study demonstrated that CAt extract treatment significantly reduced cell growth, cell cycle arrest in the G0/G1 phase, and induction of apoptosis, leading to leukemia cell death.

Keywords: Acute myeloid leukemia (AML); Apoptosis; Cedrus atlantica; Cell cycle.

MeSH terms

  • Acute Disease
  • Animals
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cedrus / chemistry*
  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • HL-60 Cells
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Plant Extracts
  • Vascular Endothelial Growth Factor A
  • Caspases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9