Mitochondrial damage by a new antitumour agent furanonaphthoquinone derivative in human cervical cancer HeLa cells.
The intracellular ultrastructural changes induced by the new antitumour agent 2-methylnaphtho[2,3-b]furan-4,9-dione (FNQ3) were investigated in human cervical cancer HeLa cells in comparison with normal cervix cells. The normal cells were isolated from cervixes surgically resected from myoma patients and were keratin positive. FNQ3 at 3-5 micrograms ml-1 selectively damaged the HeLa cell mitochondria followed by rough-surfaced endoplasmic reticulum resulting in cell death. In contrast, normal cells remained unaffected at that concentration but were damaged by 20 micrograms ml-1 FNQ3. The FNQ3-induced tumour cell toxicity was inhibited 52% and 36% by trolox and a water-soluble fraction of the antioxidative substance AOB, respectively. The results indicated that FNQ3 is selectively toxic to HeLa cells at approximately eight times that of normal cells in terms of mitochondrial alteration and free radical formation.
Pan
J
J
Department of Anatomy, Kanazawa Medical University, Ishikawa, Japan.
Hirai
K I
KI
Simamura
E
E
Koyama
J
J
Shimada
H
H
Kuwabara
S
S
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects*; D002839:Chromans / Q000494:pharmacology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D007633:Keratins / Q000032:analysis; D008928:Mitochondria / Q000187:drug effects* / Q000648:ultrastructure; D009285:Naphthoquinones / Q000494:pharmacology* / Q000633:toxicity
C106805:2-methylnaphtho(2,3-b)furan-4,9-dione; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D009285:Naphthoquinones; D007633:Keratins; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid