Prostaglandins are formed from arachidonic acid through the activities of cyclooxygenase (COX) and subsequent downstream enzymes. Two closed related forms of COXs were discovered which are identified as COX1 and COX2 and both isoenzymes can transform arachidonic acid into prostaglandins, however, differ in their physiological roles. COX1 is the constitutively expressed enzyme, on the other hand, COX2 is an inducible form and is expressed in response to growth factors or physiological stimuli as well as inflammatory resultant in the synthesis of prostaglandins which are mediating the pain and supporting the inflammation process. Furthermore, COX2 also plays a role in angiogenesis among certain cancers and in the developing of Alzheimer’s disease (AD). According to recent studies, COX2 is expressed abundantly in these diseases. Studies also suggest that COX2 inhibitors could effectively reduce the risk of developing Alzheimer’s disease. Recent studies indicated that overexpression of COX2 is associated with the development of cancers and a rise of COX2 levels is a common finding of cancer formation. COX2 inhibitors, such as non-steroidal anti-inflammatory drugs (NSAID's) play anti-cancer effect and also are able to prevent cancer development according to numerous clinical therapy studies. Therefore, it is a new hope to treat or to prevent cancers through the inhibition of COX2 functions or decreasing COX2 protein expression levels. Nowadays many COX2 inhibitors have been discovered. We ought to search natural COX2 inhibitors existence in plants and we found that Boehme- ria nivea extract (BNE-101) could effectively decreased COX2 protein expression levels in cancer cell lines. Furthermore, BNE-101 could suppress the production of signal molecule related to tumor cells growth, such as bcatenin, and decrease the activities of growth regulatory proteins, such as phospho-AKT. These data suggested that BNE-101 could play roles to inhibit tumor cells growth. We performed the soft agar assay and proved that BNE-101 could inhibit tumor cells growth in a anchorage-independent growth condition. In this study, we also found that BNE-101 decreased the protein expression levels of P-glycoprotein (P-gp), an efflux pump, which is located on cell membrane to regulate multidrug resistance (MDR) through recognizing different chemotherapeutic agents and transporting them out of membrane. Therefore, BNE-101 has great potential on regulating P-gp protein expression levels and reducing drug resistant in cancer cells. Overall, we found that BNE-101 could effectively decrease inflammation, inhibit cancer cell growth as well as reduce P-gp proteins mediated MDR. It is therefore BNE-101 is effective in the prevention and treatment of cancer.

Key Words: BNE-101, β-catenin, COX2, P-glycoprotein