Angiogenesis is an essential process in the growth, development, and transition of tumors from dormancy to proliferating state. Resveratrol (RSV), as a natural polyphenolic compound, is claimed to be effective in regulating angiogenesis. This study aimed to evaluate the impact of RSV onthe angiogenesis process in HUVECs (human umbilical vein endothelial cells) alone and co-cultured with Jurkat cells. The effects of RSV on HUVECs and Jurkat cell viability and apoptosis were measured by MTT and Annexin-V/PI methods. HUVECs were co-cultured with pre-treated Jurkat cells and incubated for 24 h, 48 h and 72 h. The angiogenesis process in HUVECs and Jurkat cells alone and in co-culture models was investigated by analyzing the expression of VEGF, VEGFR-2, and Interleukin-8 (IL-8) employing qPCR and ELISA. RSV at low concentration (40 µM) had no significant effects on apoptosis rate of HUVECs, but higher concentrations (80-160 µM) increased apoptosis in co-culture method and HUVECs alone. RSV significantly reduced VEGFR2 and IL-8 gene expression also, IL-8 protein concentration in HUVECs, but the effects of this drug in the HUVECs-Jurkats co-culture were different. Expression of VEGF in Jurkat cells increased following treatment with RSV. RSV had direct anti-angiogenic effects on HUVECs. Unexpectedly its indirect effects were not significant on HUVECs-Jurkats co-culture. Results of our study showed, RSV may be effective in anti-angiogenesis therapy, but in some situations, it may induce angiogenesis. So, appropriate concentrations should achieve to minimize the unpredicted effects of RSV.
Keywords: Angiogenesis Inhibitors; Interleukin-8; Resveratrol; VEGF; VEGFR2; co-culture.