Major drawbacks to present-day
cancer chemotherapy are its intrinsic lack of selectivity for tumour cells, resulting in severe damage to normal rapidly dividing cells, and the widespread emergence of drug resistance. Here experimental evidence is presented demonstrating that
PB-100, a
beta-carboline alkaloid, selectively inhibits in vitro multiplication of human
BCNU-resistant
glioblastoma cells (U251), but has no effect on normal astrocyte (CRL 1656) multiplication.
PB-100 activity is dose-dependent. In the presence of
ferritin or CaCl2, which are highly mitogenic for
glioblastoma cells, higher doses of the
alkaloid are required to inhibit multiplication completely.
PB-100 is one of several compounds which were selected for their specific action on
cancer DNA and cells, together with lack of activity on normal
DNA and cells. Both the selectivity of
PB-100 and its ability to overcome drug resistance stem from its effect on
cancer DNA secondary structure. This activity is described and discussed, and therapeutic applications are mentioned.