RESUMO
Considering the high metastatic potential of colorectal cancer (CRC), the inhibition of metastasis is important for anti-CRC therapy. Agrimonia pilosa Ledeb (A. pilosa) is a perennial herbaceous plant that is widely distributed in Asia. The extracts of A. pilosa have shown diverse pharmacological properties, such as antimicrobial, anti-inflammatory, and antitumor activities. In the present study, the antimetastatic activity of A. pilosa was evaluated. Methanol extraction from the roots of A. pilosa was performed by high-performance liquid chromatography (HPLC) and 12 fractions were obtained. Among these, fraction 4 showed the most potent inhibitory effect on the migration of colon cancer cells. Using LC-HR MS analysis, quercetin and quercitrin were identified as flavonoids contained in fraction 4. Like fraction 4, quercetin and quercitrin effectively inhibited the migration and invasion of RKO cells. While the level of E-cadherin was increased, the levels of N-cadherin and vimentin were decreased by the same agents. Although they all activate the p38, JNK, and ERK signaling pathways, only SP600125, an inhibitor of the JNK pathway, specifically inhibited the effect of fraction 4, quercetin, and quercitrin on cell migration. An in vivo experiment also confirmed the antitumor activity of quercetin and quercitrin. Collectively, these results suggest that A. pilosa and its two flavonoids, quercetin and quercitrin, are candidates for the antimetastatic treatment of CRC.
RESUMO
Oxidative stress and inflammation play critical roles in the development of cardiovascular diseases. Cinnamaldehyde (CA) is a natural compound from Cinnamomum cassia, and its anticancer, antimicrobial and antiinflammatory activities have been widely investigated. In the present study, the cytoprotective and antiinflammatory effects of CA on H2O2 or tumor necrosis factor (TNF)αexposed human umbilical vein endothelial cells (HUVECs) were examined. CA and its natural derivative, 2methoxycinnamaldehyde (MCA), markedly increased the cellular protein level of heme oxygenase1 (HO1) and promoted the translocation of nuclear factor erythroid 2related factor 2 (Nrf2) to the nucleus. CAmediated Nrf2/HO1 activation protected the HUVECs from H2O2induced oxidative stress, which promotes apoptosis. HO1 depletion by siRNA attenuated the CAmediated cell protective effects against oxidative stress. Additionally, CA markedly inhibited the adhesion of U937 monocytic cells to HUVECs by decreasing the expression level of vascular cell adhesion protein 1 (VCAM1). An in vivo experiment confirmed the antiinflammatory effects of CA, as lipopolysaccharide (LPS)induced inflammatory cell infiltration was effectively inhibited by the compound. Overall, these observations suggest that CA may be used as a therapeutic agent for oxidative stressmediated cardiovascular diseases, such as atherosclerosis.