Ganoderic acids suppress growth and angiogenesis by modulating the NF-?B signaling pathway in breast cancer cells

Abstract

It has been demonstrated that ganoderma acids suppress growth, angiogenesis and invasiveness of highly invasive and metastatic breast cancer cells in vitro and vivo. However, the mechanism of action of ganoderma acids in breast cancer remains unknown. In the present study, we looked into the effect of ganoderic acid Me (GA-Me) on cellular phenotypes and tumor growth in the MDA-MB-231 breast cancer cell line. The results indicated the GA-Me inhibited nuclear factor kappaB (NF-κB) activity at 24 h in MDA-MB-231 cells. When MDAMB- 231 cells were stimulated with tumor necrosis factor-alpha (TNF-α), the inhibitory effects of GA-Me were still maintained. We demonstrated that GA-Me inhibited proliferation and invasion and induced apoptosis in MDA-MB-231 cells via suppressing the NF-κB activity. However, GA-Me did not inhibit the phosphorylation and degradation of IkappaB-α (IkB-α). GA-Me down-regulated the expression of various NF-κB-regulated genes including genes involved in cell proliferation (c-Myc and cyclin D1), anti-apoptosis (Bcl-2), invasion (MMP-9) and angiogenesis (VEGF, interleukin (IL)-6 and -8). I.P. administration of GA-Me inhibited tumor growth of MDA-MB-231 cells in vivo. Our results demonstrated that GA-Me inhibited proliferation, angiogenesis, invasion and induced apoptosis in MDA-MB-231 cells via suppressing NF-κB activity and the expression profile of its downstream genes. These findings provide evidence for a novel role of GA-Me in the prevention and treatment of breast cancer by its ability to modulate the NF-κB signaling pathway.

Licochalcone A Suppresses Migration and Invasion of Human Hepatocellular Carcinoma Cells through Downregulation of MKK4/JNK via NF-κB Mediated Urokinase Plasminogen Activator Expression

“…Several genes involved in tumor metastasis have also been identified as being regulated by NF-κB [19]. The promoter of MMPs and uPA is highly conserved and was shown to contain multiple functional elements, including NF-κB elements [20]–[21]. Some studies demonstrated that NF-κB promotes the migration and metastasis of HCC cells [22], cervical cancer cells [23], and breast cancer cells [24] through an upregulation of MMPs and uPA.…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…It induces mitochondriadependent apoptosis in human cervical carcinoma HeLa cells in vitro (30). Ganoderic acid can also inhibit growth and angiogenesis of human breast cancer cell line MDA-MB-231 by modulating the NF-κB signaling pathway (31). On the other hand, ganoderic acid can enhance chemosensitivity of human hepatocellular carcinoma (HCC) cell line HepG2 to cisplatin by inhibiting the JAK-STAT3 signaling pathway (32).…”

Ganoderic acid B’s influence towards the therapeutic window of trifluoperazine (TFP)

“…Ganoderic acids, the oxygenated lanostane-type triterpenoids isolated from Ganoderma lucidum, have been reported to exhibit multiple biochemical and pharmacological activities, such as anti-tumor 2,3 , cardioprotective and liver protection activity 4,5 . The development of the compounds needs the adverse effects and in vivo elimination information, besides the pharmacologically therapeutic role.…”