Cytotoxicity of Monascus pigments and their derivatives to human cancer cells.

Six pigments were separated from Monascus product, and some derivatives were chemically synthesized. The cytotoxicity of different Monascus pigments to various human cancer cells (SH-SY5Y, HepG2, HT-29, BGC-823, AGS, and MKN45) was evaluated. Rubropunctatin showed the greatest anticancer effect within the tested compounds. The inhibition effect of rubropunctatin was higher than that of taxol on the growth of the human gastric cancer cell SH-SY5Y (P<0.05), BGC-823 (P<0.01), AGS (P<0.01), and MKN45 (P<0.05). On the other hand, its cytotoxicity to the normal human gastric epithelial cell GES-1 was less than that of taxol (P<0.01). The experimental data demonstrated that rubropunctatin was a valuable compound with high anticancer activity, which could offer better therapeutic benefits than taxol. Cell apoptosis stages were assayed by annexin V-EGFP/PI staining experiments using flow cytometry. The data showed that 87.63% of tested BGC-823 cells entered the early phase of apoptosis when treated with 5 microM rubropunctatin for 24 h. A drug concentration-dependent cell apoptosis was observed. The analysis of the relationship between pharmaceutical activity and the chemical structure of the tested compounds led to the conclusion that 6-internal ether, 4-carbonyl, and conjugated double bonds in the tricyclic structure of rubropunctatin were necessary to the anticancer effect, whereas the difference of C2H4 in the side chain showed little influence. Rubropunctatin could be supplied as a precursor compound in the development of a new natural anticancer reagent.