Breast cancer is one of the most significant causes of female
cancer death worldwide.
Paclitaxel, an extensively used
breast cancer chemotherapeutic has limited success due to drug resistance. 2-[(E)-3-naphtalen-2-yl-but-2-enoylamino]-
benzoic acid (
BIBR1532), a small molecule pharmacological inhibitor of
telomerase activity, can inhibit human
cancer cell proliferation as well. Thus, to enhance
breast cancer treatment efficacy, we studied the combination of
BIBR1532 and
paclitaxel in
breast cancer cell lines. Cell viability assays revealed that
BIBR1532 or
paclitaxel alone inhibited proliferation in a dose-dependent manner, and combining the drugs synergistically induced growth inhibition in all breast cell lines tested independent of their p53, ER, and HER2 status. The
drug combination also synergistically inhibited colony formation of MCF-7 cells in a dose-dependent manner.
Annexin V-PI staining and Western blot assays on PARP cleavage and
caspase-8 and
caspase-3 revealed that
BIBR1532 in combination with
paclitaxel was more potent than either agent alone in promoting MCF-7 cell apoptosis. Cell cycle analysis indicated that
BIBR1532 induced a G1 phase arrest and
paclitaxel arrested cells at the G2/M phase. The
drug combination dramatically blocked S cells from entering the G2/M phase. Our results suggest the potential of
telomerase inhibition as an effective
breast cancer treatment and that used in conjunction with
paclitaxel; it may potentiate
tumor cytotoxicity.