Ellipticine derivative induces potent cytostatic effect in acute myeloid leukaemia cells.

A panel of novel ellipticine isomers were designed and synthesised with the aim of evaluating their anti-cancer effects on selected leukaemia cell lines. A preliminary NCI 60-cell screen demonstrated that these compounds display promising anti-tumour activity across a number of different cell types. We have consequently examined the effect of these derivatives in detail on the Acute Myeloid Leukaemia (AML) cell line, MV4-11. Cell cycle analyses revealed that the compounds had a range of distinctive cell cycle effects. 7-Hydroxyisoellipticine showed the most promise with respect to cytostatic activity. We demonstrated that this compound inhibited proliferation of leukaemia cells by preventing cells from progressing from G2 phase into mitosis over a period of 24 h at a concentration of 5 µM. Our research suggests that this is mediated by an induction of reactive oxygen species (ROS), which in turn activates the DNA damage response pathway. As a result of the activation of p53, cyclin B1 is inhibited. The induction of this pathway leads to apoptosis which is seen at 48 h using the same dose of 7-hydroxyisoellipticine. This study provides for the first time detailed cellular information on the potential use of isoellipticines as chemotherapeutic agents.

Unilateral facial nerve paralysis following an infected lower third molar.

The authors report the case of a 35-year-old Arab man who presented with unilateral facial nerve palsy in the presence of an infected lower third molar. The paralysis occurred within hours of the development of a left-sided facial swelling. Surgical removal of the tooth and drainage of the abscess produced significant improvement in facial nerve function, and total resolution occurred prior to clinical follow-up 10 days later. The authors discuss the aetiology of this hemifacial paralysis and its significance as a clinical sign of third molar odontogenic infection.