Diverse Effects of β-Carotene on Secretion and Expression of VEGF in Human Hepatocarcinoma and Prostate Tumor Cells

Abstract

Oral administration of β-carotene (BC) was found to exert opposite effects on plasma levels of vascular endothelial growth factor (VEGF) in two animal models. One study in nude mice injected via tail vein with hepatocarcinoma SK-Hep-1 cells showed that BC decreases the plasma VEGF level, whereas the other study in nude mice injected subcutaneously with prostate tumor PC-3 cells showed that BC increases the plasma VEGF level. Herein we investigated whether BC (0.5–20 μM) possesses diverse effects on VEGF secretion in SK-Hep-1, PC-3 and melanoma B16F10 cells. We found that incubation of SK-Hep-1 cells with BC (1–20 μM) for 6 h significantly decreased VEGF secretion, whereas BC (1–10 μM) significantly increased the VEGF secretion in PC-3 cells. However, these effects disappeared at 12 h of incubation. Similar effects occurred in VEGF mRNA and protein expression after treatment of SK-Hep-1 and PC-3 cells with BC for 6 h. In contrast, BC (0.5–20 μM) did not affect mRNA and protein expression and secretion of VEGF in B16F10 cells. We also found that the proliferation of SK-Hep-1 and B16F10 cells was significantly inhibited by 20 μM BC at 6 and 12 h of incubation, whereas the proliferation of PC-3 cells was significantly inhibited by 20 μM BC at 12 h of incubation. In summary, the present study demonstrated the tumor-specific effect of BC on VEGF secretion in different cancer cell lines.

Carotenoids: biochemistry, pharmacology and treatment

“…In general, α‐carotene and lycopene, but not β‐carotene, were inversely associated with the risk of PCa (Wang et al ., ). Moreover, it was suggested that tomatoes can play a modest role in suppressing PCa (Chen et al ., ). Meta‐analysis of four studies in men randomized to receive lycopene did not show any significant decrease in the incidence of benign prostatic hyperplasia (BPH) or PCa.…”

Recent Progress in Discovering the Role of Carotenoids and Their Metabolites in Prostatic Physiology and Pathology with a Focus on Prostate Cancer—A Review—Part I: Molecular Mechanisms of Carotenoid Action

“…The impact on PC-3 proliferation was in line with findings from the VEGF measurement—for 12 h of incubation with 1–5 μM BC the proliferation was slightly increased. Only when treated with 20 μM of BC, cells showed a 20% decreased proliferation [ 95 ].…”

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“…Lycopene significantly upregulates interleukin (IL)-12 and interferon (IFN)-γ [123,133]. IL-12 is a key negative regulator of angiogenesis by stimulating IFNγ, which mediates production of anti-angiogenic chemokines [134]. Other studies have found that lycopene may have an anti-angiogenic impact by inhibiting matrix metalloproteinase 2 (MMP-2) and urokinase-type plasminogen activator (UPA) through vascular endothelial growth factor receptor (VEGFR)-2 mediated PI3K-Akt and ERK/p38 signaling pathways, leading to decreased tube formation [123,132,135,136].…”