Anti-proliferative and proteasome inhibitory activity of Murraya koenigii leaf extract in human cancer cell lines

Proteasome inhibition has been demonstrated to be a promising strategy for cancer therapy. The chymotrypsin-like activity of the 20S catalytic unit of the 26S proteasome is known to be critical for cancer cell survival. Inhibition of the proteasomal activity leads to tumor cell death. Murraya koenigii Spreng a medically important herb of Asian origin, is rich in phenolic content, and dietary polyphenols are known to act as proteasome inhibitors. This study was aimed at testing the cytotoxic and proteasomal inhibitory potential of M. koenigii leaf extract in four different human cell lines namely; colon, prostate, liver and cervical cancer. The cytotoxicity of M. koenigii leaf extract was tested by the MTT assay, inhibition of growth by colony formation assay and inhibition of the chymotrypsin-like (Ch-L) activity of the 26S proteasome using a specific fluorogenic substrate by fluorometry. There was a dose-dependent decrease in cell viability/proliferation with M. koenigii leaf extract treatment in all the cell lines tested. In line with the cell viability data there was a dose-dependent decrease in growth as observed by decreased colony formation in the cell lines tested. M. koenigii extract decreased the Ch-L activity of the endogenous proteasome in both intact cells and cell extracts in all the four cancer cell lines. Our results suggest that the proteasome is a target for M. koenigii leaf extract in various cancer cell lines and that inhibition of the proteasome may be one of the mechanisms responsible for its anticancer potential