title: Combination of albendazole and 2-methoxyestradiol significantly improves the survival of HCT-116 tumor-bearing nude mice.
abstract: BACKGROUND
  Albendazole (ABZ) is a microtubule-targeting anthelmintic with a remarkable activity against a variety of human cancer cells. In this study, we examined if the antitumor activity of ABZ could be enhanced by its combination with other microtubule-binding agents.
  
  
  METHODS
  The interactions between ABZ and microtubule-binding agents, paclitaxel, vinblastine, colchicine, and 2-methoxyestradiol were characterized using median effect analysis method in HCT-116 colorectal cancer cells and DU145 prostate cancer cell line. The mechanism underlying the synergistic interaction related to tubulin polymerization and apoptosis was then investigated. Finally, the effect of the combination therapy on the survival of HCT-116 tumor-bearing nude mice was evaluated.
  
  
  RESULTS
  Among the tested drugs, a synergistic anti-proliferative effect was observed with the combination of low concentrations of ABZ plus colchicine and ABZ plus 2-methoxyestradiol (2ME). Exploring the mechanism of the interaction between ABZ and 2ME revealed that the combination therapy synergistically activated the extrinsic pathway of apoptosis. Consistent with in vitro results, the combination of low concentration of ABZ with 2ME prolonged the survival of mice-bearing HCT-116 tumors. High concentration of ABZ in combination with 2ME, however, proved to be less effective than ABZ alone.
  
  
  CONCLUSIONS
  The combination of low doses of ABZ and 2ME has shown promising results in our pre-clinical model. Additionally, the finding that the combination of two microtubule-binding agents that share the same binding site can act synergistically may lead to the development of new therapeutic strategies in cancer treatment.
authors: Cancer Research Laboratories, Department of Surgery, University of New South Wales, St, George Hospital, Sydney, NSW, Australia. s3199267@unsw.edu.au
authors: Anahid
authors: A
authors: Ehteda
authors: Peter
authors: P
authors: Galettis
authors: Krishna
authors: K
authors: Pillai
authors: David L
authors: DL
authors: Morris
mesh_terms: D000077584:2-Methoxyestradiol; D015766:Albendazole / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003078:Colchicine / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003603:Cytotoxins / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality; D050257:Tubulin Modulators / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D003603:Cytotoxins; D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol; D015766:Albendazole; D003078:Colchicine