Ginsenoside Rd attenuates breast cancer metastasis implicating derepressing microRNA-18a-regulated Smad2 expression

Abstract

Metastasis remains a major cause of mortality and poor prognosis in breast cancer patients. Anti-metastatic therapies are in great need to achieve optimal clinical outcome in breast cancer patients. Panax Notoginseng Saponins (PNS) has previously been shown to inhibit breast cancer metastasis in mouse. Here the potential anti-metastatic effect of one of the chemical compounds of PNS, ginsenoside Rd (Rd), was further evaluated in mouse mammary carcinoma 4T1 cells. The results revealed that Rd treatment dose-dependently suppressed cell migration and invasion in cultured 4T1 cells. In 4T1 cell-inoculated mice, Rd treatment led to decreased number of tumor lesions in lungs in both spontaneous and experimental metastasis models. Rd treatment resulted in increased expression of Smad2 in cultured 4T1 cells and in tumors grown from inoculated 4T1 cells. Rd treatment decreased the expression of microRNA (miR)-18a in cultured 4T1 cells and in tumors derived from inoculated 4T1 cells. Smad2 was further verified to be a direct target of miR-18a in 4T1 cells. The significant impact of Rd on counteracting miR-18a-medidated downregulation of Smad2 expression was also demonstrated. Together, the current work shows for the first time that Rd treatment attenuates breast cancer metastasis in part through derepressing miR-18a-mediated Smad2 expression regulation.

Ginsenoside Rd Inhibits the Metastasis of Colorectal Cancer via Epidermal Growth Factor Receptor Signaling Axis

“…In addition, the antimetastatic effects of ginsenoside Rd in liver cancer via blocking the MAPK signaling pathway and inducing focal adhesion formation have been indicated . In addition, ginsenoside Rd also counteracts miR‐18a and mediates the downregulation of Smad2 expression, leading to the suppression of breast cancer metastasis . In the present study, we demonstrated that ginsenoside Rd inhibited migration and invasion of CRC cells in a dose‐dependent manner.…”

Panax ginseng and Panax quinquefolius : From pharmacology to toxicology

“…Hou et al, 2017;Yan et al, 2017;Wang et al, 2016;Xie et al, 2016 20(S)-PPT Re (2S,3R,4R,5R,6S)-2-[(2R,3R,4S,5S,6R)-2-[[(3S,5R,6S,8R,9R,10R,12R,13R,14R,17S)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-[(2S)-6-methyl-2-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) oxan-2-yl]oxyhept-5-en-2-yl]-2,…”

Recent Progress on the Molecular Mechanisms of Anti-invasive and Metastatic Chinese Medicines for Cancer Therapy

“…In addition, ginsenoside Rd (Rd), one of the chemical compounds in Panax Notoginseng Saponins, has been investigated for its anti-metastatic property recently. The results showed that Rd treatment inhibited the migratory and invasive ability of breast cancer both in vitro and in vivo via suppressing miR-18a-mediated Smad2 expression [96].…”