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Liposomes Containing (-)-Gossypol-Enriched Cottonseed Oil Suppress Bcl-2 and Bcl-xL Expression in Breast Cancer Cells

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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.

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ACKNOWLEDGMENTS & DISCLOSURES

This study is supported by NIH Grant R01 ES-015212 and Cotton Inc. Grant 06–864.

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Authors and Affiliations

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

    Hong Li, Longzhu Piao, Yicheng Mao, Youngah Cho & Robert J. Lee

  2. Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, Columbus, Ohio, 43210, USA

    Hong Li, Pingping Xu, Weiping Ye, Saiyi Zhong, Shu-Hong Lin & Young C. Lin

  3. Division of Medicinal Chemistry and Pharmacognosy College of Pharmacy, The Ohio State University, Columbus, Ohio, 43210, USA

    Samuel K. Kulp

  4. OSU Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, 43210, USA

    Robert J. Lee & Young C. Lin

  5. NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, Columbus, Ohio, 43210, USA

    Yicheng Mao, L. James Lee & Robert J. Lee

Authors
  1. Hong Li
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  2. Longzhu Piao
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  3. Pingping Xu
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  4. Weiping Ye
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  5. Saiyi Zhong
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  6. Shu-Hong Lin
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  7. Samuel K. Kulp
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  8. Yicheng Mao
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  9. Youngah Cho
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  10. L. James Lee
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  11. Robert J. Lee
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  12. Young C. Lin
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Corresponding authors

Correspondence to Robert J. Lee or Young C. Lin.

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Li, H., Piao, L., Xu, P. et al. Liposomes Containing (-)-Gossypol-Enriched Cottonseed Oil Suppress Bcl-2 and Bcl-xL Expression in Breast Cancer Cells. Pharm Res 28, 3256–3264 (2011). https://doi.org/10.1007/s11095-011-0498-2

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  • DOI: https://doi.org/10.1007/s11095-011-0498-2

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