Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

Abstract

Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression.

Rutin inhibits proliferation, attenuates superoxide production and decreases adhesion and migration of human cancerous cells

“…The inhibitory effect of rutin on cell migration is likely due to the reduced attachment to ECM proteins observed in the presence of this flavonoid. The same effect was observed with others flavonoids against lung cancer A549 cells and human colorectal adenocarcinoma DLD1 and SW480 cells [78,79].…”

Apigenin in cancer therapy: anti-cancer effects and mechanisms of action

“…In the human lung cancer cell line A549, apigenin exerted anti-migration and anti-invasion effects by suppressing the phosphorylation of AKT and targeting the PI3K/AKT signaling pathway [ 47 ]. And in the colorectal cancer cell lines DLD1 and SW480, Dai et al proved that apigenin could inhibit cell migration, invasion, and metastasis through modulating the NEDD9/Src/AKT cascade [ 48 ].…”

Flavonoids inhibit cell proliferation and induce apoptosis and autophagy through downregulation of PI3Kγ mediated PI3K/AKT/mTOR/p70S6K/ULK signaling pathway in human breast cancer cells

“…In vitro studies indicate that anticancer activities of flavonoids may be related to inhibiting cell proliferation, adhesion, and invasion, inducing cell differentiation, cell cycle arrest, and apoptosis, etc. 6 , 7 . In vivo studies demonstrate that flavonoids could inhibit carcinogenesis by affecting the molecular events in the initiation, promotion, and progression stages 8 .…”