## 3 Discussion
Indeed, it has been reported that RSV at 10 and 50 uM concentrations significantly increased tubule formation in the HCAEC-human coronary arteriolar endothelial cells on the matrigel, and enhanced the expression of the VEGF protein [35]. [PERSON] et al. [36] described similar properties of RSV. The treatment of cerebral endothelial cells (THBMEC) with RSV promoted proliferation, migration, and tube formation in the matrigel assays. However, in these studies, RSV was applied at 5 uM concentration. Conversely, RSV did not affect the proliferation and apoptosis of retinal pigmented cells (ARP-19 cell line). It was also confirmed by [PERSON] and [PERSON] [37]. It still remains unexplained why and how RSV induces apoptosis in cancer cell lines and endothelial HECa10 cell lines, but not in the non-tumor cells. RSV induces cell cycle arrest in many cancer cell lines, such as A549, U87, U138, PC-3, and primary cell cultures, such as vascular smooth muscle cells and primary rat hepatocytes [38; 39; 40; 41; 42]. Here, we did not find significant changes in cell cycle phases in both endothelial and retinal pigment cells; however, we noticed a dose-dependent tendency for cell accumulation in the S phase. We observed about 10% more cells in the S phase upon 100 uM RSV treatment than in the control. [PERSON] et al. [36] also showed that, in the human cerebral microvascular endothelial cell line, the increase in the proportion of the S phase and the decrease in the G0/G1 phase proportion in the cell cycle of these cells was observed. [PERSON] et al. [43] reported that the RSV induced the G1-phase arrest in A431 cells (human epidermoid carcinoma) mediated by WAF-1/p21, which blocked the following cyclin-cdk complexes: cyclin E-cdk2, cyclin D1/D2-cdk6, and cyclin D1/D2-cdk4. We observed a similar increased cell percentage in the G0/G1 phase in HECa10 cells at 100 uM RSV concentration. However, this effect seems to be related rather to cell death and not to cell cycle arrest. We showed that the RSV treatment (1-10 uM) reduced the VEGF concentration in both analysed cell lines. Moreover, 50-100 uM RSV reduced the VEGF level secreted by the epithelial ARPE-19 cells (significant reduction) but not by the endothelial HECa10 cells. Interestingly, the retinal pigment epithelial ARPE-19 cells produced significantly higher levels of VEGF than endothelial HECa10 cells. These differences between the two cell types can be extremely important in the eye's microenvironment reorganisation and intercellular interactions. These results are similar to the data obtained from other laboratories. RSV, in a dose-dependent manner in concentrations between 10 and 50 \(\upmu\)M, suppressed VEGF-A and VEGF-C secretion induced by inflammatory cytokines in the RPE cells and decreased VEGF mRNA level [44]. Also, [PERSON] et al. [45] observed that the 10-30 \(\upmu\)M RSV decreased the concentration of VEGF in the ovarian cancer SKOV-3 cell line. Moreover, RSV may have negated improvement of the myocardial perfusion and the arteriolar density achieved by the VEGF treatment in the hypercholesterolemia swine model of chronic ischemia [46]. RSV may also affect the biological activity of VEGF. Recently, [PERSON] et al. (2019) showed that RSV might attenuate angiogenesis by inhibiting receptor signaling [47]. In contrast to the VEGF, the bFGF concentration in HECa10 cells was not affected by the RSV treatment (except for 50 \(\upmu\)M concentration) and it was increased in epithelial cells at 1-100 \(\upmu\)M concentrations of RSV. The elevated level of the FGF2 mRNA was also observed by [PERSON] et al. [48] in rats supplemented daily for 6 weeks with 22.04 mg/kg of RSV. Furthermore, [PERSON] et al. [49] observed that RSV (5-15 \(\upmu\)M) inhibited the angiogenic response of cultured endothelial F-2 cells to the vascular endothelial growth factor but not to the basic fibroblast growth factor.