title: The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer.
abstract: Despite recent advances in therapy, breast cancer remains the second most common cause of death from malignancy in women. Chemotherapy plays a major role in breast cancer management, and combining chemotherapeutic agents with nonchemotherapeutic agents is of considerable clinical interest. Cucurbitacins are triterpenes compounds found in plants of the Cucurbitaceae family, reported to have anticancer and anti-inflammatory activities. Previously, we have shown antiproliferative activity of cucurbitacin B (CuB) in breast cancer, and we hypothesized that combining CuB with chemotherapeutic agents can augment their antitumor effect. Here, we show that a combination of CuB with either docetaxel (DOC) or gemcitabine (GEM) synergistically inhibited the proliferation of MDA-MB-231 breast cancer cells in vitro. This antiproliferative effect was accompanied by an increase in apoptosis rates. Furthermore, in vivo treatment of human breast cancer orthotopic xenografts in immunodeficient mice with CuB at either low (0.5 mg/kg) or high (1 mg/kg) doses in combination with either DOC (20 mg/kg) or GEM (12.5mg/kg) significantly reduced tumor volume as compared with monotherapy of each drug. Importantly, no significant toxicity was noted with low-dose CuB in combination with either DOC or GEM. In conclusion, combination of CuB at a relatively low concentration with either of the chemotherapeutic agents, DOC or GEM, shows prominent antiproliferative activity against breast cancer cells without increased toxicity. This promising combination should be examined in therapeutic trials of breast cancer.
authors.affiliation: Division of Hematology and Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Aribi
authors.forename: Sigal
authors.initials: S
authors.lastname: Gery
authors.forename: Dhong Hyun
authors.initials: DH
authors.lastname: Lee
authors.forename: Nils H
authors.initials: NH
authors.lastname: Thoennissen
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Thoennissen
authors.forename: Rocio
authors.initials: R
authors.lastname: Alvarez
authors.forename: Quoc
authors.initials: Q
authors.lastname: Ho
authors.forename: Kunik
authors.initials: K
authors.lastname: Lee
authors.forename: Ngan B
authors.initials: NB
authors.lastname: Doan
authors.forename: Kin T
authors.initials: KT
authors.lastname: Chan
authors.forename: Melvin
authors.initials: M
authors.lastname: Toh
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Said
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077143:Docetaxel; D004357:Drug Synergism; D005260:Female; D006801:Humans; D051379:Mice; D043823:Taxoids / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology* / Q000633:toxicity; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D014315:Triterpenes; C041246:cucurbitacin B; D003841:Deoxycytidine; D000077143:Docetaxel; D000093542:Gemcitabine