Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

Abstract

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.

The relationship between previous pulmonary tuberculosis and risk of lung cancer in the future

“…In monocyte subsets, there had basal expression of COX-2 and 5-LOX, and the expression increased significantly after stimulation with purified protein derivative (PPD) of Mycobacterium tuberculosis [ 82 ]. Recent evidence display that upregulation of COX-2 promotes tumorigenesis by promoting the metastasis signal affecting MMP-9 activity, it attenuates cancer cell migration and invasion via Akt, NF-Κb, and AP-1 signal pathways [ 83 ]. In addition to affecting tumor metastasis, upregulation of COX-2 is correlated with inhibition of apoptosis and increased intratumoral microvessels growth [ 84 – 86 ].…”

Rosmarinic Acid and Related Dietary Supplements: Potential Applications in the Prevention and Treatment of Cancer

“…After extracting oil from the seeds, RA can be enriched by 70% ethanol and ethyl acetate extraction. The RA-enriched fraction reduced reactive oxygen species (ROS) and inhibited invasion through the NF-κB pathway in A549 cells [ 21 , 22 ].…”

Mechanism of action of CTRP6 in the regulation of tumorigenesis in the digestive system (Review)

“…One of the specific mechanisms by which the PI3K/Akt pathway promotes tumorigenesis is through the dysregulation of inflammatory mediators and immunity. It has been shown that rosmarinic acid subsequently prevents lung tumor invasion by reducing the production of inflammatory factors, such as IL-6, IL-8, TNF-α and cyclooxygenase-2, by inhibiting Akt phosphorylation ( 26 ). We speculate that this mechanism of action of the PI3K/Akt pathway is equally applicable during the pathogenesis of digestive tumors.…”

“…Abnormal lipid metabolism leads to disturbances in adipokine secretion, which is strongly associated with tumorigenesis and tumor progression ( 41 ). Obesity due to abnormal lipid metabolism is an independent risk factor for tumorigenesis and tumor development in a variety of liver, pancreatic, ovarian and colorectal cancer types ( 26 , 40 , 42 ). The role of CTRP6 in glycolipid metabolism has been extensively studied ( 43 ).…”