Poster Presentation Advances in Neuroblastoma Research Congress 2016

Inhibition of the growth factor midkine in neuroblastoma by an Okinawan agricultural product (#358)

Shinya Ikematsu 1 , Hirotsugu Shiroma 1 , Shoma Tsubota 2 , Satoshi Kishida 2 , Kenji Kadomatsu 2
  1. National Institute of Technology, Okinawa College, Nago, OKINAWA, Japan
  2. Biochemistry, Nagoya Graduate School of Medicine, Nagoya, Aichi, Japan

The growth factor midkine(MK) is overexpressed in various cancers, including neuroblastoma (Ikematsu et al,Brit J Cancer,2003;Ikematsu et al,Cancer Sci,2008). MK is involved in anti-apoptosis and cell growth. At Okinawa prefecture in Japan that is located in a subtropical oceanic climate zone, many agricultural products are paid attentions since they have various functions such as anti-oxidative activity, tyrosinase inhibition activity and antitumor activity. In this study, we screened Okinawa natural products for antitumor activity using MK as an indicator by enzyme-linked immunosorbent assay. We obtained 7 candidate materials with suppressive activity of MK expression in human neuroblastoma cells. Among the candidates, the suppression of MK expression of Jabuticaba(Myricaria cauliflora) leaf ethanol extract was the most remarkable. The Jabuticaba extract downregulated MK mRNA expression, reduced cell survival, and increased caspase 3/7 activity. Furthermore,  the extract inhibited antigen-antibody reaction of MK-ELISA, suggesting that Jabuticaba extracts blocked MK action by masking MK. The results suggested that Jabuticaba leaf ethanol extract exerts apoptosis-inducing activity through suppression of MK expression and prevention of the binding between MK and its receptor(s) on cell surface.