Chalcone Derivatives Inhibit Human Platelet Aggregation and Inhibit Growth in Human Bladder Cancer Cells

Abstract

In an effort to develop potent cyclooxygenase-1 (COX-1) inhibitors used as anticancer agent, a series of 2′,5′-dimethoxychalcones was screened to evaluate their antiplatelet effect on human washed platelets suspension. Compound 2 exhibited potent inhibition of human washed platelet aggregation induced by collagen, significantly inhibited collagen-and arachidonic acid-induced thromboxane B 2 release, and revealed inhibitory effect on COX-1 activity. Molecular docking studies showed that 1, 2, and 4 were bound in the active site of COX-1. These indicated that the antiplatelet effect of these compounds were mainly mediated through the suppression of COX-1 activity and reduced the thromboxane formation. To investigate the mechanistic action of COX-1 inhibitor enhanced the cytotoxic effect against human bladder cancer cells, NTUB1, we assessed the cytotoxic effect of 2 against NTUB1. Treatment of NTUB1 cells with various concentrations of 2 led to a concentration-dependent increase of cell death and decrease of reactive oxygen species levels. The flow-cytometric analysis showed that 2 induced a G1 phase cell cycle arrest but did not accompany an appreciable sub-G1 phase in NTUB1 cells. In addition, compound 2 increased p21 and p27 expressions and did not inhibit the expression of COX-1 in NTUB1 cells. Our results suggested that 2 enhanced cell growth inhibition or antiproliferative activity in NTUB1 cells through G1 arrest by COX-1 independent mechanism.

Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome

“…Evidence from epidemiologic studies supports a potential role for some flavonoids in the reduction of cardiovascular risk. For instance, flavonoids are able to prevent against endothelial dysfunction through averting oxidation of low-density lipoproteins (LDL) [ 6 ], platelet aggregation and adhesion [ 7 ], and smooth muscle cell migration and proliferation [ 8 ]. Moreover, according to recent data aiming to evaluate association between dietary flavonoid intake and cardiovascular risk through analyses of prospective cohort studies, it has been reported that intakes of epigallocathechin gallate (EGCG) (relative risk: 0.87; 95% confidence interval: 0.80, 0.95) were inversely associated with the risk of cardiovascular diseases [ 9 ].…”

Chemopreventive effect of chalcone derivative, L2H17, in colon cancer development

“…Synthetic analogs and derivatives of the molecule are increasingly getting into focus due to their promising therapeutic potential. Chalcone derivatives are reported to exhibit anti-cancer effects in several cancer cell lines, such as human acute leukemia cells [ 8 ], colon cancer cells [ 9 , 10 ], human bladder cancer cells [ 11 ], and lung cancer cells [ 12 ]. In addition, as anticancer therapeutic agents, chalcones have advantages such as poor interaction with DNA and low risk of mutagenesity [ 13 ].…”

Novel Insights into the Mode of Action of Vasorelaxant Synthetic Polyoxygenated Chalcones

“…By inhibiting the angiotensin-converting enzyme (ACE) and inducing high vasodilation, the anti-hypertensive effect of amino-chalcones has been demonstrated in vitro and in vivo on rats, rabbits, and dogs [25,26]. Several molecular targets such as cyclooxygenase [27] and potassium channels [28], metabolism pathways such as triacylglycerol synthesis pathway [29][30][31] and pro-angiogenic properties [32] have also been identified to explain the potential role of chalcones in the prevention and/or treatment of cardiovascular diseases. However, all these effects have been mainly highlighted with functionalized chalcones bearing amino, prenyl or sulfonyloxy groups and little data are available for polyoxygenated chalcones [25].…”