Induced apoptosis and necrosis by 2-methylfuranonaphthoquinone in human cervical cancer HeLa cells

3-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) has been reported to be more c ytotoxic to human malignant tumor cell lines than are the corresponding nor mal epithelial cells. Therefore, we examined the dose response of FNQ3 agai nst human cervical cancer HeLa cells in culture. When 1.25 mg/ml FNQ3 was a pplied, apoptosis was induced, as determined by an immunohistochemical stai ning of fragmented genome DNA and cell profiles. Significant inhibition of Bcl-2 oncogene protein expression by the same concentration of FNQ3 also wa s demonstrated by an immunohistochemical staining method to visualize the e xpressed cells and Western blot in polyacrylamide gel electrophoresis. Flow -cytometric spectra showed S-phase arrest in cell cycles and the appearance of sub-G(1) phase consistent with apoptosis. On the other hand, concentrat ions of 5 mu g/ml or more of FNQ3 induced necrosis. These results show that FNQ3 may act as an antitumor agent to induce apoptosis by affecting Bcl-2 expression and cell cycles, or necrosis as the result of primary mitochondr ial injuries.