A combination of the telomerase inhibitor, BIBR1532, and paclitaxel synergistically inhibit cell proliferation in breast cancer cell lines

Abstract

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.

Inhibition of telomerase using BIBR1532 enhances doxorubicin-induced apoptosis in pre-B acute lymphoblastic leukemia cells

“…Our results also delineated that BIBR1532 augments doxorubicin-induced apoptosis and its antiproliferative effect, as evidenced by the increased externalization of phosphatidylserine (PS), elevated sub-G1 cell population, and decreased number of inhibitor-treated viable cells. Consistently, Shi et al showed that combination of BIBR1532 and paclitaxel synergistically inhibits cell proliferation in breast cancer cell lines [30]. In another study, it was reported that simultaneously treatment of APL-derived NB4 cells with ATO-plus-BIBR1532 resulted in caspase-3 activation and eventually increased apoptotic cell death [31].…”

Biological behavior exploration of a paclitaxel-eluting poly-l-lactide-coated Mg–Zn–Y–Nd alloy intestinal stent in vivo

“…Even though previous research report refered to that the clinical efficacy of paclitaxel was affected by drug resistance, in view of its excellent antiproliferation property in the treaty of breast cancer paclitaxel was regarded as one of the effective antiproliferative drugs. 24 At the same time, it has been reported in literatures that both paclitaxel and sirolimus can effectively inhibit neointimal hyperplasia of coronary artery within a month dose range, and the effect has a certain degree of safety. [24][25][26][27] It can effectively reduce the degree of vascular restenosis.…”

“…24 At the same time, it has been reported in literatures that both paclitaxel and sirolimus can effectively inhibit neointimal hyperplasia of coronary artery within a month dose range, and the effect has a certain degree of safety. [24][25][26][27] It can effectively reduce the degree of vascular restenosis. Therefore, paclitaxel and sirolimus are commonly used in drug-eluting stents for the treatment of coronary stenosis.…”

Effects of telomerase inhibitor on epigenetic chromatin modification enzymes in malignancies

“…The study of Shi et al 17 shows that BIBR1532 inhibited cell proliferation and induced a G1-phase cell cycle arrest in breast cancer cell lines. In this study, the IC 50 values of BIBR1532 were found to be 8.56 and 32 μM at the 72nd hour, respectively.…”