Pinocembrin Inhibits the Proliferation and Metastasis of Breast Cancer via Suppression of the PI3K/AKT Signaling Pathway

Abstract

The survival rate of breast cancer (BC) patients remains poor, thus the identification of safe and effective new drugs is crucial to improve therapeutic outcomes and overall survival. Pinocembrin (PCB), a pharmacologically active ingredient of Pinus heartwood, Eucalyptus, Euphorbia, Populus, and Sparattosperma leucanthum, has been widely applied for the treatment of various diseases and possesses anticancer activities. In vitro assays were performed to investigate the antiproliferation and antimetastasis activities of PCB in BC cells. A tumorigenesis assay with the use of murine BC models was performed to assess the antiproliferation activities of PCB in vivo. Moreover, the molecular mechanisms underlying the anticancer activities of PCB in BC cells were explored. The results showed that the anti-inhibitory and antiproliferation activities of PCB in BC might involve cell cycle (G2/M phase) arrest and apoptosis. PCB downregulated the expression levels of proteins involved in cell cycle progression and apoptosis, including cyclinB1, Cdc2, PARP1, Bcl-2, and survivin, and upregulated protein levels of cleaved PARP1, cleaved caspase3, cleaved caspase9, and BAX. In a murine subcutaneous tumor model, PCB suppressed the growth of MCF-7 cells in vivo. Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. Mechanistically, PCB administration was correlated to suppression of the PI3K/AKT signaling pathway. Inhibition of the proliferation of BC cells by PCB involved cell cycle (G2/M phase) arrest and apoptosis in vitro and in vivo. Low concentrations of PCB also significantly inhibited the migration and invasion abilities of BC cells. These findings suggest that PCB might be an effective agent for treatment of BC patients.

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

“…Some other polyphenols have also proven effective as anti-metastatic agents. Pinocembrin, one of the major water-insoluble flavonoids in propolis, inhibited EMT and metastasis by preventing NF-κB translocation to MMP promoter sites [ 385 , 386 ]. Furthermore, at non-cytotoxic concentrations, pinocembrin suppressed the TGF-β1-induced cell-matrix adhesion, invasion, and migration of human retinoblastoma Y-79 cells.…”

Functionalized Sulfur-Containing Heterocyclic Analogs Induce Sub-G1 Arrest and Apoptotic Cell Death of Laryngeal Carcinoma In Vitro

“…In silico studies predicted that the analog BP might be a better inhibitor of the CYP1A2 enzyme than DYRK1A is. Studies have found that an antioxidant molecule named Pinocembrin also have potential antiproliferation activity against breast cancer cells [ 49 ], and also was found to be a CYP1A2 inhibitor [ 50 ]. From the results obtained in this study, we can strongly suggest that BP and EP action resembles the mechanism of action of Pinocembrin by having an antioxidant potential, and they possibly could bind to CYP1A2, thus exerting anticancer activity.…”

Alpinia katsumadai Hayata induces growth inhibition and autophagy‑related apoptosis by regulating the AMPK and Akt/mTOR/p70S6K signaling pathways in cancer cells

“…These findings indicated that AKH mainly contains chalcones and diarylheptanoids. Pinocembrin exerts anti-inflammatory, anti-bacterial and anticancer effects ( 47 , 48 ). Studies have shown that pinocembrin inhibits the proliferation, migration and invasion of breast cancer cells at non-cytotoxic concentrations by inhibiting the STAT3 signaling pathway ( 48 ).…”

“…Pinocembrin exerts anti-inflammatory, anti-bacterial and anticancer effects ( 47 , 48 ). Studies have shown that pinocembrin inhibits the proliferation, migration and invasion of breast cancer cells at non-cytotoxic concentrations by inhibiting the STAT3 signaling pathway ( 48 ). Cardamonin is the main flavonoid derived from AKH and exerts anti-proliferative effects against various cancer cells ( 49 ).…”