Login to Access Video or Poster Abstract: MP81-18
Sources of Funding: none

Introduction

Although sex hormones may play a role in angiogenesis, the direct effects of sex hormones on vascular endothelial cells remain to be characterized. Thus, the aim of this study was to examine the effects of sex hormones and androgen inhibitors on cell proliferation in Human Umbilical Vein Endothelial Cells (HUVECs).

Methods

We analyzed the expression of androgen receptor (AR) and enzymes relevant to the action of androgens in HUVECs and prostate cancer cell lines. Furthermore, we analyzed the effect of testosterone (T), dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and several androgen inhibitors (enzalutamide, abiraterone, dutasteride) in HUVECs. Viability of HUVECs was determined using the WST-1 assay.

Results

We observed that the protein level of AR in HUVECs was lower than that of the prostate cancer cell lines (LNCap, C4-2). Our results indicated that treatment with T, DHEA, DHT, enzalutamide, and abiraterone (Fig. 1) caused decreased cell proliferation at high doses. Dutasteride did not have an effect on HUVEC viability. Enzalutamide and abiraterone decreased HUVEC proliferation, including when in proliferation-inducing conditions with VEGF. To ascertain their potential androgenic activity, we cultured HUVECs with the steroid precursor ¹³C-[2,3,4]-progesterone (13C-Prog), and analyzed the subsequent biosynthesis of ¹³C-[2,3,4]-17-hydroxyprogesterone (13C-17-OHP) and ¹³C-[2,3,4]-androstenedione (13C-Adione) by liquid chromatography/mass spectrometry (LC/MS/MS). LC/MS/MS analysis enabled detection of 13C-17-OHP and 13C-A-dione in HUVEC cells. Furthermore, we observed that CYP17A1 has dual activities, mediated by 17α-hydroxylase and 17, 20-lyase, in HUVECs.

Conclusions

The present results demonstrated that HUVECs may undergo apoptosis mediated by sex hormones. Enzalutamide and abiraterone have an in vitro anti-proliferative effect on HUVECs, but not dutasteride. Thus, the anti-angiogenic activity of enzalutamide and abiraterone may have a therapeutic effect on prostate cancer.

Funding

none