New potential beneficial effects of actein, a triterpene glycoside isolated from Cimicifuga species, in breast cancer treatment

Abstract

Actein is a triterpene glycoside isolated from the rhizomes of Cimicifuga foetida (Chinese herb “shengma”) which could inhibit the growth of breast cancer cells. Nevertheless, the effect of actein on angiogenesis, which is an essential step for tumor growth and metastasis, has never been reported. Hence, this study aimed to investigate the in vitro and in vivo effects of actein on angiogenesis using human microvascular endothelial cells (HMEC-1), matrigel plug and tumor-bearing mouse models. Our results showed that actein significantly inhibited the proliferation, reduced the migration and motility of endothelial cells, and it could suppress the protein expressions of VEGFR1, pJNK and pERK, suggesting that JNK/ERK pathways were involved. In vivo results showed that oral administration of actein at 10 mg/kg for 7 days inhibited blood vessel formation in the growth factor-containing matrigel plugs. Oral actein treatments (10–15 mg/kg) for 28 days resulted in decreasing mouse 4T1 breast tumor sizes and metastasis to lungs and livers. The apparent reduced angiogenic proteins (CD34 and Factor VIII) expressions and down-regulated metastasis-related VEGFR1 and CXCR4 gene expressions were observed in breast tumors. Our novel findings provide insights into the use of actein for development of anti-angiogenic agents for breast cancer.

Structure-Guided Identification of Black Cohosh (Actaea racemosa) Triterpenoids with In Vitro Activity against Multiple Myeloma

“…The study moreover found that the p53-dependent mitochondrial signaling pathway contributes to the mechanism of apoptosis. A more recent study in a murine breast tumor-bearing model demonstrated that actein (1) exhibits anti-angiogenic and immunomodulatory effects and decreased tumor size and metastasis in lung and liver [19].…”

A systems pharmacology approach to determine the mechanisms of action of pleiotropic natural products in breast cancer from transcriptome data

“…Actein is a widely studied natural triterpene glycoside that has recently attracted attention in breast cancer due to its effects on various biological processes in cancer 16, 47–49 . In this study, cell death and cell cycle roles of TGF-beta, PI3K-Akt-mTOR and NRF2 pathways were up-regulated while proliferation roles of TGF-beta pathway were down-regulated.…”

Benefit–risk profile of black cohosh (isopropanolic Cimicifuga racemosa extract) with and without St John’s wort in breast cancer patients

“…Embryonic stem cell-expressed RAS was identified as a potent oncogenic driver in the HER2-positive MMTV model, acting via hyperactivation of the phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, which stimulates tumor cell proliferation and metastasis and induces therapy resistance 70,71 . Recently, actein was identified as an effective inhibitor of the PI3K/AKT/mTOR pathway, showed anti-angiogenic effects in vitro, and decreased breast tumor size and metastasis in vivo 72,73 . CR activated AMP-activated protein kinase, which is known to inhibit mTOR 74 .…”