Assessment of the Anti-invasion Potential and Mechanism of Select Cinnamic Acid Derivatives on Human Lung Adenocarcinoma Cells

Abstract

Patients with lung adenocarcinoma are often diagnosed with metastasizing symptoms and die of early and distal metastasis. Metastasis is made up of a cascade of interrelated and sequential steps, including cell adhesion, extracellular matrix degradation, cell movement, and invasion. Hence, substances carrying the ability to stop one of the metastasis-associated steps could be a potential candidate for preventing tumor cells from metastasizing and prolonging the life of cancer patients. Cinnamic acid (CA) was demonstrated to be such a candidate for human lung adenocarcinoma cells. Nevertheless, the effectiveness of CA derivatives on invasion of lung cancer cells is still unclear. The aims of this study were to explore the mechanisms underlying several select CA derivatives against invasion of human lung adenocarcinoma A549 cells. The results revealed that caffeic acid (CAA), chlorogenic acid (CHA), and ferulic acid (FA) can inhibit phorbol-12-myristate-13-acetate (PMA)-stimulated invasion of A549 cells at a concentration of ≥100 μM. The MMP-9 activity was suppressed by these compounds through regulating urokinase-type plasminogen activator (uPA), tissue inhibitor of metalloproteinase (TIMP)-1, plasminogen activator inhibitor (PAI)-1, and PAI-2; the cell-matrix adhesion was decreased by CAA only. The proposed molecular mechanism involved not only decreasing the signaling of MAPK and PI3K/Akt but also inactivating NF-κB, AP-1, and STAT3. In the present study, we selected CAA, CHA, and FA as potential inhibitors for invasive behaviors of human lung adenocarcinoma cells and disclosed the possible mechanisms. The association between structural features and anti-invasive activity of these compounds cannot be determined here and needs to be further verified.

Anti-invasive Activity against Cancer Cells of Phytochemicals in Red Jasmine Rice (Oryza sativa L.)

“…Whereas, the other phenolic compounds in the EtOAc fraction could not reduce cancer cell invasion. These results are similar to those of several studies, which have reported on the anti-metastasis property of vanillic and ferulic acid (Lirdprapamongkol et al, 2009;Tsai et al, 2013). However, the concentration of the vanillic acid and ferulic acid were present in 100 μg/ml of the EtOAc fraction did not to be sufficient doses to promote anti-invasion.…”

Down-regulation of SerpinB2 is associated with gefitinib resistance in non-small cell lung cancer and enhances invadopodia-like structure protrusions

“…The mitogen activated protein kinase (MAPK) pathway is a well-known pathway that increases cell motility and MMP secretion, leading to the protrusion of invadopodia/podosomes2433. Therefore, we also evaluated the effects of YD on the MAPK pathways in H292-Gef cells.…”

An overview on the role of dietary phenolics for the treatment of cancers

“…Furthermore, in addition to downregulating the phosphorylation of Akt kinase, Caffeic acid phenyl ester has suppressed the expression of AKT isoforms in prostate cancer cells [111]. Few other studies have also reported the therapeutic efficacy of cinnamic acid derivatives such as ferulic acid, caffeic acid and chlorogenic acids for treating cancers [112]. The data revealed that these cinnamic acid derivatives down modulate MAPK and AKT signaling pathways to inactivate the NF-kβ, AP-1 and STAT3 in lung adenocarcinomas [112].…”