Production of hydrogen peroxide and redox cycling can explain how sanguinarine and chelerythrine induce rapid apoptosis.

Sanguinarine and chelerythrine are naturally occurring benzophenanthridines with multiple biological activities. Sanguinarine is believed to be a potential anticancer agent but its mechanism of action has not been fully elucidated. We previously found that it causes oxidative DNA damage and very rapid apoptosis that is not mediated by p53-dependent DNA damage signaling.

Pharmacologic effects of ospemifene in rhesus macaques: a pilot study.

Ospemifene (Ophena) is a new selective oestrogen receptor modulator currently in phase III clinical development for treatment of post-menopausal vulvar and vaginal atrophy. In the present study, we examined the pharmacokinetics, toxicity, and DNA adduct forming potential of ospemifene in the liver and endometrium of rhesus macaques following single and subchronic dosing schedules to better understand the potential toxicologic effects of ospemifene. During single weekly dosing, six macaques were administered 35 mg/kg/week ospemifene orally for 3 weeks.

Sanguinarine causes DNA damage and p53-independent cell death in human colon cancer cell lines.

The benzophenanthridine alkaloid sanguinarine has antimicrobial and possibly anticancer properties but it is not clear to what extent these activities involve DNA damage. Thus, we studied its ability to cause DNA single and double strand breaks, as well as increased levels of 8-oxodeoxyguanosine, in human colon cancer cells and found DNA damage consistent with oxidation. Since the tumor suppressor p53 is frequently involved in inducing apoptosis following DNA damage we investigated the effect of sanguinarine in wild type, p53-mutant and p53-null colon cancer cell lines.

Two closely related nickel complexes have different effects on DNA damage and cell viability.

Nickel is considered a weak carcinogen. It is known to interact with DNA and DNA-binding proteins. The ability of certain nickel compounds to cleave DNA has been exploited mainly for research purposes and less for developing new anticancer drugs.