MITOCHONDRIAL DAMAGE BY A NEW ANTITUMOR AGENT FURANONAPHTHOQUINONE DERIVATIVE IN HUMAN CERVICAL-CANCER HELA-CELLS

The intracellular ultrastructural changes induced by the new antitumou r 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 resecte d from myoma patients and were keratin positive. FNQ3 at 3-5 mu g ml(- 1) selectively damaged the HeLa cell mitochondria followed by rough-su rfaced endoplasmic reticulum resulting in cell death. In contrast, nor mal cells remained unaffected at that concentration but were damaged b y 20 mu g ml(-1) FNQ3. The FNQ3-induced tumour cell toxicity was inhib ited 52% and 36% by trolox and a water-soluble fraction of the antioxi dative 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 for mation.