Antidepressant hyperforin up-regulates VEGF in CNS tumour cells

Abstract

Vascular endothelial growth factor (VEGF) is a key player in neo-angiogenesis; it sustains the progression of solid neoplasias, brain tumours included. It has recently been demonstrated that the use of antidepressants correlates with increasing VEGF levels in the central nervous system (CNS). In order to elucidate whether the most used natural antidepressant [St. John's wort (SJW) extract] modulates VEGF expression, possible relationship between ≤ μM hyperforin (Hyp, the bioactive component in SJW) and VEGF in CNS tumours has been now examined in medulloblastoma and glioblastoma cells. Real-time PCR and ELISA revealed that under Hyp VEGF expression increased more than three fold in DAOY medulloblastoma cells; while, U87 glioblastoma cells – constitutively expressing high VEGF levels – showed no significant differences. Moreover, Hyp induced endothelial pro-angiogenic behaviour in a multi-parametric Matrigel colonisation assay, and down-modulation of pro-MMP-2 and pro-MMP-9 activities as measured by gelatin zymography. Should these results be confirmed in vivo for this and other types of CNS tumour, the antidepressant use of SJW extracts must be carefully re-considered, in particular for brain tumour patients.