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Pharm Res. 2011 Dec;28(12):3256-64. doi: 10.1007/s11095-011-0498-2. Epub 2011 Jun 28.

Liposomes containing (-)-gossypol-enriched cottonseed oil suppress Bcl-2 and Bcl-xL expression in breast cancer cells.

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1
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, Ohio 43210, USA.

Abstract

PURPOSE:

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.

METHODS:

(-)-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.

RESULTS:

(-)-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.

CONCLUSIONS:

Findings suggest that (-)-GPCSO liposomes warrant continued investigation as a chemosensitizer for breast cancers exhibiting Bcl-2-/Bcl-xL-mediated drug resistance.

PMID:
21710341
PMCID:
PMC3809120
DOI:
10.1007/s11095-011-0498-2
[Indexed for MEDLINE]
Free PMC Article
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