Effective strategies to reverse or prevent chemotherapeutic resistance are required before
cancer therapies can be curative.
Telomerase is the
ribonucleoprotein responsible for de novo synthesis and maintenance of telomeres, and its activity is predominantly observed in
cancer cells. The
telomerase enzyme has been successfully inhibited or inactivated to sensitize cells to cellular stresses; however, no studies have determined yet the effect of combining a pharmacological inhibitor of
telomerase catalysis and traditional chemotherapeutics for the treatment of
drug-sensitive or
drug-resistant
cancers. Here, we describe the effect of 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-
benzoic acid (
BIBR1532), a small-molecule inhibitor of
telomerase catalytic activity, on
drug-resistant
leukemia and
breast cancer cells and their parental counterparts when treated in combination with chemotherapeutics. We observed that BIBR1532-treated cells show progressive telomere shortening, decreased proliferative capacity, and sensitization to chemotherapeutic treatment. These effects are telomere length-dependent, because cells insensitive to
BIBR1532 or cells released from
telomerase inhibition did not demonstrate changes in growth ability or
drug sensitivity. Our novel observations suggest that pharmacological
telomerase inhibition in combination
therapy may be a valid strategy for the treatment of both
drug-sensitive and
drug-resistant
cancers.