title: Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo.
abstract: Cucurbitacins are a group of diverse triterpenoid substances isolated from plants with medicinal properties. One particularly potent family member is cucurbitacin B (CuB). The antiproliferative effects of CuB against human breast cancer cells were tested. Six human breast cancer cell lines were examined because they represent a diverse mix of breast cancer subtypes varying in expression of estrogen receptor (ER), Her2/neu, and p53 mutation. The antiproliferative effect of CuB were also studied in vivo. The effective dose inhibiting 50% growth (ED(50)) was between 10(-8) M and 10(-7) M for this collection of breast cancer cell lines. These cells underwent rapid morphologic changes after 15-20 min exposure to CuB (5 x 10(-7) M), which was associated with disruption of the microtubules and F-actin, as observed by confocal microscopy. Human MDA-MB-231 (ER-, p53 mutated) breast cancer cells were orthotopically implanted into the breasts of nude mice who intraperitoneally received either CuB 1.0 mg/kg or vehicle. Tumor volume was reduced by 55% in the group that received CuB for 6 weeks compared with vehicle controls. No apparent organ tissue damage was observed by pathological assessment. Interestingly, the experimental mice had lower serum glucose levels, consistent with use of CuB as an antidiabetic drug in China. This drug appears to be a third in a family of drugs targeting the microtubules (taxanes [e.g. taxol], vinca alkaloid [e.g. vincristine], and now CuB). Our in vitro and in vivo results suggest that CuB may be an effective, new approach for the treatment of ER-, Her2/neu amplified, and p53 mutant breast cancers.
authors.affiliation: Division of Hematology/Oncology, Cedars-Sinai Medical Center/University of California at Los Angeles, School of Medicine, California 90048, USA. wakimoto@remus.dti.ne.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Wakimoto
authors.forename: Dong
authors.initials: D
authors.lastname: Yin
authors.forename: James
authors.initials: J
authors.lastname: O'Kelly
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Beth
authors.initials: B
authors.lastname: Karlan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.forename: Hongtao
authors.initials: H
authors.lastname: Xing
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C041246:cucurbitacin B