Identification of a structure specific Bcl-2 phosphorylating homoisoflavone molecule from Vietnamese coriander (Polygonatum odoratum) that induces apoptosis and G2/M cell cycle arrest in breast cancer cell lines

Bcl-2 is an anti-apoptotic protein which is over-expressed in many cancers. Modulating Bcl-2 expression is one of the most important strategies in the combat of cancer. We have isolated and identified a structure specific homoisoflavone from Vietnamese coriander (Polygonatum odoratum or Solomon seal) root which induces Bcl-2 phosphorylation, thereby causing mitotic arrest in breast cancer cells. Bioassay-directed fractionations resulted in a biologically active fraction for Bcl-2 phosphorylation. HPLC separation followed by mass spectrometry and NMR studies identified two compounds. We currently combine the chemistry and biological activity of Vietnamese coriander extracts by using bioassay directed fractionation to identify the structure specific Bcl-2 phosphorylating molecules, as well as their molecular mechanism of action. Only one molecule was responsible for Bcl-2 phosphorylation; it was identified as 2,3-dihydro3-[(15-hydroxyphenyl) methyl]-5,7-dihydroxy-6(8-dimethyl-4H-1-benzopyran-4-one) or 8-methyl-dihydrobenzopyranone (8-methyl-DBP, MW 314). The effect on Bcl-2 was structure specific, because 2,3 dihydro3-[(15-hydroxyphenyl) methyl]-5,7-dihydroxy-6-methyl-8-methoxy-4H-1-benzopyran-4-one or 8-methoxy-dihydrobenzopyranone (8-methoxy-DBP, MW 330), in contrast to 8-methyl-DBP, was not capable of Bcl-2 phosphorylation. Pure 8-methyl-DBP induced Bcl-2 phosphorylation in breast tumor cells, causes G2/M cell cycle arrest, up regulates the expression of p21 and p53 proteins and decreases cell viability demonstrated by a clonogenic assay. Therefore, these data demonstrate that Vietnamese coriander root contains 8-methyl-dihydrobenzopyrone (8-methyl-DBP, MW 314), which induces Bcl-2 phosphorylation, apoptosis, and G2/M cell cycle arrest in breast tumor cells.