The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer
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The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer. / Aribi, Ahmed; Gery, Sigal; Lee, Dhong Hyun; Thoennissen, Nils H; Thoennissen, Gabriela B; Alvarez, Rocio; Ho, Quoc; Lee, Kunik; Doan, Ngan B; Chan, Kin T; Toh, Melvin; Said, Jonathan W; Koeffler, H Phillip.
in: INT J CANCER, Jahrgang 132, Nr. 12, 15.06.2013, S. 2730-7.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer
AU - Aribi, Ahmed
AU - Gery, Sigal
AU - Lee, Dhong Hyun
AU - Thoennissen, Nils H
AU - Thoennissen, Gabriela B
AU - Alvarez, Rocio
AU - Ho, Quoc
AU - Lee, Kunik
AU - Doan, Ngan B
AU - Chan, Kin T
AU - Toh, Melvin
AU - Said, Jonathan W
AU - Koeffler, H Phillip
N1 - Copyright © 2012 UICC.
PY - 2013/6/15
Y1 - 2013/6/15
N2 - 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.
AB - 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.
KW - Animals
KW - Antineoplastic Agents, Phytogenic
KW - Apoptosis
KW - Bone Marrow Cells
KW - Breast Neoplasms
KW - Cell Line, Tumor
KW - Cell Proliferation
KW - Deoxycytidine
KW - Drug Synergism
KW - Female
KW - Humans
KW - Mice
KW - Taxoids
KW - Triterpenes
KW - Tumor Burden
KW - Xenograft Model Antitumor Assays
U2 - 10.1002/ijc.27950
DO - 10.1002/ijc.27950
M3 - SCORING: Journal article
C2 - 23165325
VL - 132
SP - 2730
EP - 2737
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 12
ER -
