Abstract
Saikosaponin A (SSA), a main triterpenoid saponin component from Radix Bupleurum, has been revealed to have a variety of pharmacological activities. However, whether SSA can inhibit angiogenesis, a key step in solid tumor progression, remains unknown. In this study, we demonstrated that SSA could powerfully suppress the proliferation, migration, and tube formation of human umbilical vein endothelial cells. SSA also significantly inhibited angiogenesis in the models of the chick embryo chorioallantoic membrane and Matrigel plugs. Moreover, SSA was found to inhibit tumor growth in both orthotopic 4T1 breast cancer and subcutaneous HCT-15 colorectal tumor by the inhibition of tumor angiogenesis. Western blot assay indicated the antiangiogenic mechanism of SSA in the suppression of the protein phosphorylation of VEGFR2 and the downstream protein kinase including PLCγ1, FAK, Src, and Akt. In summary, SSA can suppress angiogenesis and tumor growth by blocking the VEGFR2-mediated signaling pathway.
Highlights
Saikosaponin A (SSA, Figure 1A), a main triterpenoid saponin component from Radix Bupleurum, has been widely investigated for its multiple pharmacological activities, such as antidepressant (Guo et al, 2020), immunoregulatory (Qi et al, 2021), and anti-inflammatory properties (He et al, 2016; Du et al, 2018; Zhou et al, 2019; Piao et al, 2020)
Compared to human umbilical vascular endothelial cells (HUVECs), tumor cells (4T1 and HCT-15) were less sensitive to SSA. 3.4- ∼ 7.4-fold higher viability of the 4T1 and HCT-15 cells was maintained after treatment with 10–100 μM SSA
The activated tumor endothelial cells are more sensitive to chemotherapeutic drugs than tumor cells, offering a choice for specific antiangiogenic therapy (Kerbel and Kamen, 2004)
Summary
Saikosaponin A (SSA, Figure 1A), a main triterpenoid saponin component from Radix Bupleurum, has been widely investigated for its multiple pharmacological activities, such as antidepressant (Guo et al, 2020), immunoregulatory (Qi et al, 2021), and anti-inflammatory properties (He et al, 2016; Du et al, 2018; Zhou et al, 2019; Piao et al, 2020). SSA regulates Th1/Th2 balance in tumors (Zhao et al, 2019) and generates microbicidal neutrophils to reduce cancer chemotherapy–induced neutropenia infection (Qi et al, 2021); both of them can benefit from antitumor therapy. It remains elusive whether SSA can directly suppress angiogenesis, the hallmark and a key step in solid tumor progression (Hanahan and Weinberg, 2011). More than 10 antiangiogenic drugs, including small kinase inhibitors (sunitinib, sorafenib, pazopanib, etc.), antibodies (bevacizumab and ramucirumab), and fusion proteins
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