Liposomes Containing (-)-Gossypol-Enriched Cottonseed Oil Suppress Bcl-2 and Bcl-xL Expression in Breast Cancer Cells
| Autor: | Robert J. Lee, Hong Li, Young C. Lin, L. James Lee, Samuel K. Kulp, Shu-Hong Lin, Pingping Xu, Weiping Ye, Youngah Cho, Saiyi Zhong, Longzhu Piao, Yicheng Mao |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Cottonseed Oil Paclitaxel Cell Survival bcl-X Protein Chemosensitizer Mice Nude Pharmaceutical Science Breast Neoplasms Bcl-xL Biology Article Mice chemistry.chemical_compound In vivo Cell Line Tumor Internal medicine Tumor Cells Cultured medicine Animals Humans Pharmacology (medical) Breast Cytotoxicity Pharmacology Liposome Organic Chemistry Gossypol Antineoplastic Agents Phytogenic Gene Expression Regulation Neoplastic Endocrinology Proto-Oncogene Proteins c-bcl-2 chemistry Cell culture Liposomes Cancer research biology.protein Molecular Medicine Female Biotechnology |
| Zdroj: | Pharmaceutical Research. 28:3256-3264 |
| ISSN: | 1573-904X 0724-8741 |
| DOI: | 10.1007/s11095-011-0498-2 |
| Popis: | We have demonstrated that (-)-gossypol-enriched cottonseed oil [(-)-GPCSO] can down-regulate Bcl-2 expression in MCF-7 and primary cultured human breast cancer epithelial cells (PCHBCECs). However, this agent has not been evaluated in vivo due to its limited solubility. We aimed to develop liposomes containing (-)-GPCSO to suppress Bcl-2/Bcl-xL expression. (-)-GPCSO liposomes were prepared and evaluated for effects on breast cancer cell viability, MDA-MB-231 xenograft tumor growth, cellular Bcl-2 and Bcl-xL mRNA levels, and chemosensitivity to paclitaxel. (-)-GPCSO liposomes prepared had excellent stability. Cytotoxicity of (-)-GPCSO liposomes was significantly reduced compared to (-)-GPCSO in culture medium. Bcl-2 and Bcl-xL mRNA expression was down-regulated by (-)-GPCSO in culture medium or (-)-GPCSO liposomes in MDA-MB-231 cells. In PCHBCECs, Bcl-2 and Bcl-xL expression were down-regulated by (-)-GPCSO liposomes. (-)-GPCSO in culture medium induced only a mild reduction in Bcl-xL. In the MDA-MB-231 xenograft tumor model, (-)-GPCSO liposomes exhibited tumor-suppressive activity and significantly reduced intratumoral Bcl-2 and Bcl-xL expression. Cytotoxicity of paclitaxel was increased by pretreatment with (-)-GPCSO liposomes in MDA-MB-231 and PCHBCECs. Findings suggest that (-)-GPCSO liposomes warrant continued investigation as a chemosensitizer for breast cancers exhibiting Bcl-2-/Bcl-xL-mediated drug resistance. |
| Databáze: | OpenAIRE |
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