Celecoxib and acetylbritannilactone interact synergistically to suppress breast cancer cell growth via COX-2-dependent and -independent mechanisms

Abstract

The use of celecoxib is associated with a significant decrease in breast cancer risk. However, the long-term use of high-dose celecoxib might be limited owing to cardiovascular side effects. In this study, we found that acetylbritannilactone (ABL), extract from a Chinese medicinal herb, could reduce celecoxib dose and potentiate the growth-inhibitory effect in breast cancer cells. ABL enhanced the apoptotic effect of celecoxib in COX-2-expressing cells, but had little effect in COX-2-negative cells. The apoptosis induced by the combination treatment disappeared when COX-2 was knocked down, whereas the lack of apoptotic effects in COX-2-negative cells was reversed after COX-2 transfection. However, the combination treatment induced a G0/G1 phase arrest independent of whether or not the cells expressed COX-2. The G0/G1 arrest was attributed to a decreased expression of cyclinD1, cyclinE, CDK2 and CDK6, especially the upregulation of p21. In addition, inhibition of Akt and p38 signaling pathways was required by the synergism, as the constitutively active Akt and p38 protected cells against apoptosis and cell cycle arrest induced by the combination treatment. In vivo, administration of celecoxib and ABL were more effective than the individual agents against xenograft tumor growth. Thus, our data suggested that the combinatorial approach of celecoxib and ABL might be helpful for breast cancer treatment.

Celecoxib Enhances Radiosensitivity via Induction of G₂-M Phase Arrest and Apoptosis in Nasopharyngeal Carcinoma

“…Abundant studies indicate that celecoxib suppress cell proliferation and carcinogenesis through different mechanism [22,23]. Celecoxib is shown to suppress breast cancer cells growth through COX-dependent mechanism and the inhibitory effects are disappeared when COX-2 is knocked down [22].…”

“…Celecoxib is shown to suppress breast cancer cells growth through COX-dependent mechanism and the inhibitory effects are disappeared when COX-2 is knocked down [22]. The evidence from in vitro and in vivo experiments indicates that the underlying mechanism responsible for the anticancer activities of celecoxib involves the induction of cell apoptosis [24,25].…”

Aspirin Inhibits IKK-β-mediated Prostate Cancer Cell Invasion by Targeting Matrix Metalloproteinase-9 and Urokinase-Type Plasminogen Activator

“…Cells were plated in 24-well plates, then the cells were co-transfected with NF-κB-Luc plasmid and the internal control plasmid renilla luciferase (pRL-TK) using transfection reagent Lipofectamine 2000 (Invitrogen, Carlsbad, CA) as described previously [25]. The cells were harvested after aspirin treatment, and the luciferase activity was measured using the Dual Luciferase Reporter Assay System (Promega, Madison, WI).…”

“…Cells were treated and then the cells were prepared with lysis buffer and western blot analysis was performed [25]. The proteins were separated by 10% SDS-PAGE, then transferred onto PVDF membranes and blotted with primary antibodies against Histone H2B (1: 400), β-actin (1: 400), NF-κB p65 (1: 400), IκB-α (1: 1000), phospho-IκB-α (1: 1000), IKK-α (1: 1000), IKK-β (1: 1000) and phospho-IKK-α/β (1: 1000) at 4°C overnight, and then incubated with the secondary antibody (1: 10000) for 2 h. The blots were normalized against β-actin or Histone H2B.…”

Celecoxib inhibits insulin-like growth factor 1 induced growth and invasion in non-small cell lung cancer

“…Despite epidemiological and experimental evidence indicating an important role for the use of celecoxib, a highly selective COX-2 inhibitor, in the treatment and prevention of NSCLC (4,5), the exact mechanism remains unclear. Conversely, however, recent studies have shown that even the highly selective COX-2 inhibitors have potential side effects (6). These agents should, therefore, be used at a low dosage.…”