Bitter apricot essential oil induces apoptosis of human HaCaT keratinocytes

Int Immunopharmacol. 2016 May;34:189-198. doi: 10.1016/j.intimp.2016.02.019. Epub 2016 Mar 9.

Abstract

Psoriasis is a chronic skin disease that affects approximately 2% of the world's population. Conventional therapeutic approaches are not effective or necessarily safe for treating symptoms due to the serious side effects and resistance to currently prescribed drugs. Traditionally, in oriental medicine, apricot seed (Semen Armeniacae amarum) is used to treat skin diseases. However, the underlying mechanism of action has not been systematically elucidated. In the present study, the anti-proliferative effect of bitter apricot essential oil (BAEO) on cultured HaCaT cells was evaluated and the mechanism of action investigated. BAEO was isolated by hydrodistillation, and gas chromatography-mass spectrometry (GC-MS) analysis identified benzaldehyde (75.35%), benzoic acid (6.21%) and mandelonitrile (5.38%). HaCaT cell growth, measured by sulforhodamine B assay (SRB), was inhibited by BAEO with an IC50 value of 142.45 μg/ml. Apoptosis of HaCaT cells treated with BAEO was detected by cell cycle, flow cytometry, and western blot analyses. These measurements revealed G0/G1 cell cycle arrest, elevated numbers of early and late stage apoptotic cells, and caspases-3/8/9 and PARP activation. Z-VAD-FMK, a broad-spectrum caspase inhibitor, attenuated BAEO-induced apoptosis. Also, increased Bax and decreased Bcl-2 levels suggest that BAEO-induced apoptosis is mediated through both death receptor and mitochondrial pathways. Moreover, reduced Rel/NF-κB levels suggest that BAEO-mediated apoptosis is also associated with inhibition of the NF-κB pathway. These data suggest that BAEO is a naturally occurring material that functions as a potent pro-apoptotic factor for human keratinocytes. Thus, it is a promising candidate to treat psoriasis.

Keywords: Apoptosis; Bitter apricot; Cell cycle; HaCaT cells; NF-κB; Psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Line
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / physiology
  • Mitochondria / drug effects*
  • NF-kappa B / metabolism
  • Oils, Volatile / pharmacology*
  • Oncogene Proteins v-rel / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Prunus armeniaca / immunology*
  • Psoriasis / drug therapy*
  • Receptors, Death Domain / metabolism
  • Signal Transduction / drug effects

Substances

  • Amino Acid Chloromethyl Ketones
  • NF-kappa B
  • Oils, Volatile
  • Oncogene Proteins v-rel
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Death Domain
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Caspases