Xanafide,
a DNA-
intercalating agent and
topoisomerase II inhibitor, has previously demonstrated comparable cytotoxicity to the parent
drug amonafide (
NSC 308847). The current study was conducted to investigate further the anti-proliferative effects of
xanafide in human
breast cancer cell lines, in vitro and in vivo. The in vitro activity of
xanafide against MCF-7, MDA-MB-231, SKBR-3 and T47D cell lines was compared to that of
paclitaxel,
docetaxel,
gemcitabine,
vinorelbine and
doxorubicin. In MCF-7,
xanafide demonstrated comparable total growth inhibition (TGI) concentrations to the
taxanes and lower TGI values than
gemcitabine,
vinorelbine and
doxorubicin. MCF-7 (oestrogen receptor (ER)+/p53 wild-type) was the most sensitive cell line to
xanafide. MDA-MB-231 and SKBR-3 exhibited similar sensitivity to
xanafide. T47 D (ER+/p53 mutated), showed no response to this agent. The in vivo activity of
xanafide was further compared to that of
docetaxel in MCF-7 and MDA-MB-231 cell lines using the hollow fibre assay.
Xanafide was slightly more potent than
docetaxel, at its highest dose in MCF-7 cell line, whereas
docetaxel was more effective than
xanafide in MDA-MB-231 cell line. Our results show that there is no relationship between sensitivity of these cell lines to
xanafide and cellular levels of both
isoforms of
topoisomerase II and suggest that ER and p53 status and their crosstalk may predict the responsiveness or resistance of
breast cancer patients to
xanafide.