The triterpenoid cucurbitacin B augments the antiproliferative activity of chemotherapy in human breast cancer
| Autor: | Melvin Toh, Dhong Hyun Lee, Ngan B. Doan, H. Phillip Koeffler, Sigal Gery, Gabriela B. Thoennissen, Quoc Ho, Ahmed M. Aribi, Rocio Alvarez, Nils H. Thoennissen, Kunik Lee, Jonathan W. Said, Kin Tak Chan |
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| Rok vydání: | 2012 |
| Předmět: |
Cancer Research
medicine.medical_treatment Apoptosis Bone Marrow Cells Breast Neoplasms Docetaxel Pharmacology Deoxycytidine Article Mice Breast cancer Cell Line Tumor Animals Humans Medicine Cytotoxicity Cell Proliferation Chemotherapy business.industry fungi Cancer Drug Synergism medicine.disease Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Gemcitabine Triterpenes Tumor Burden Oncology Toxicity Female Taxoids business medicine.drug |
| Zdroj: | International Journal of Cancer. 132:2730-2737 |
| ISSN: | 0020-7136 |
| Popis: | 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 non-chemotherapeutic agents is of considerable clinical interest. Cucurbitacins are triterpenes compounds found in plants of the Cucurbitaceae family, reported to have anti-cancer and anti-inflamatory 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 anti-tumor 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 (12.5 mg/kg) significantly reduced tumor volume as compared to 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. |
| Databáze: | OpenAIRE |
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