Induced apoptosis and necrosis by 2-methylfuranonaphthoquinone in human cervical cancer HeLa cells.
2-Methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) has been reported to be more cytotoxic to human malignant tumor cell lines than are the corresponding normal epithelial cells. Therefore, we examined the dose response of FNQ3 against human cervical cancer HeLa cells in culture. When 1.25 mg/ml FNQ3 was applied, apoptosis was induced, as determined by an immunohistochemical staining of fragmented genome DNA and cell profiles. Significant inhibition of Bcl-2 oncogene protein expression by the same concentration of FNQ3 also was demonstrated by an immunohistochemical staining method to visualize the expressed cells and Western blot in polyacrylamide gel electrophoresis. Flow-cytometric spectra showed S-phase arrest in cell cycles and the appearance of sub-G1 phase consistent with apoptosis. On the other hand, concentrations of 5 microg/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 mitochondrial injuries.
Pan
J
J
Department of Anatomy, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
Simamura
E
E
Koyama
J
J
Shimada
H
H
Hirai
K I
KI
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D002584:Cervix Uteri / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D008928:Mitochondria / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D009336:Necrosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016196:S Phase; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000378:metabolism*
C106805:2-methylnaphtho(2,3-b)furan-4,9-dione; D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D004247:DNA