A combination of the telomerase inhibitor, BIBR1532, and paclitaxel synergistically inhibit cell proliferation in breast cancer cell lines.
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.
Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201210, China.
Yi
Y
Shi
Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201210, China.
Lin
L
Sun
Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201210, China.|School of Life Science and Technology, ShanghaiTech University, 319 Yueyang Road, Shanghai, 200031, China.
Ge
G
Chen
Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201210, China.
Dongyan
D
Zheng
Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201210, China. lil@sari.ac.cn.
Li
L
Li
Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai, 201210, China. weiwg@sari.ac.cn.|School of Life Science and Technology, ShanghaiTech University, 319 Yueyang Road, Shanghai, 200031, China. weiwg@sari.ac.cn.
Wanguo
W
Wei
D062365:Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology*; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors
D062365:Aminobenzoates; C458523:BIBR 1532; D009281:Naphthalenes; D019098:Telomerase; D017239:Paclitaxel
Apoptosis; BIBR1532; Breast cancer; Paclitaxel; Telomerase inhibitor