Differences in intracellular sites of action of Adriamycin in neoplastic and normal differentiated cells

Abstract

These results suggest that ADM exerts cytostatic effects on neoplastic and normal undifferentiated cells through the inhibition of DNA synthesis by DNA intercalation, and cytotoxic effects on neoplastic cells through the accumulation of reactive oxygen species resulting from low scavenger enzyme activities. The cytotoxic effects on normal differentiated cells may be related to the high levels of production of reactive oxygen species due to high mitochondrial NADH-cytochrome c reductase activity.

Sanguinarine cytotoxicity on mouse melanoma K1735-M2 cells—Nuclear vs. mitochondrial effects

“…Other factors such as direct effects of the drug on the organelle after initial nuclear effects can also account for mitochondrial dysfunction and lead cells to die upon caspase activation despite the fact that the p53-Bax pathway is not operating. The data presented suggest that SANG acts as a DNA damaging agent, showing also collateral damage to mitochondrial bioenergetics, in a fashion similar to doxorubicin, a powerful anti-cancer agent which acts both at the mitochondrial and nuclear level [57]. SANG should be considered as a potential novel chemotherapeutic for the treatment of aggressive melanoma, with further tests required to identify potential advantages of combinations with other molecules.…”

Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity

“…With one noticeable exception, regarding a selective induction of lipid peroxidation by 1 M DOX in mouse lymphocytic leukemia cell line L1210 but not in pig kidney proximal tubular epithelial cell line LLC-PK1 (Kiyomiya et al, 2001a), there is apparent evidence to conclude that anthracyclines do not induce lipid peroxidation in cancer cells at clinically relevant concentrations. Under defined conditions, a dissociation actually exists between anthracycline cytotoxicity and lipid peroxidation.…”

Melatonin increased vitamin C and antioxidant enzyme values in the plasma,heart, liver, and kidney of Adriamycin-treated rats

“…However, the mechanism of Adriamycin toxicity is not completely understood. Several mechanisms have been suggested to explain Adriamycin cytotoxicity (Gewirtz et al, 1999), including stabilization of DNA-topomerase complex (Guano et al, 1999), intercalation into DNA (Kiyomiya et al, 2001), and increasing of reactive oxygen species and semiquinone radicals induced by Adriamycin (Kalyanaraman et al, 2002;Othman et al, 2008). Adriamycin is transformed to semiquinone free radicals by the NADPH-cytochrome P450 microsomal system.…”