caa a22 4500 445312629 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0498-2 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0498-2 Liposomes Containing (-)-Gossypol-Enriched Cottonseed Oil Suppress Bcl-2 and Bcl-xL Expression in Breast Cancer Cells [Elektronische Daten] [Hong Li, Longzhu Piao, Pingping Xu, Weiping Ye, Saiyi Zhong, Shu-Hong Lin, Samuel Kulp, Yicheng Mao, Youngah Cho, L. Lee, Robert Lee, Young Lin] 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. Springer Science+Business Media, LLC, 2011 (-)-gossypol nationallicence Bcl-2 nationallicence Bcl-xL nationallicence chemoresistance nationallicence liposomes nationallicence Li Hong Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut Piao Longzhu Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut Xu Pingping Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut Ye Weiping Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut Zhong Saiyi Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut Lin Shu-Hong Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut Kulp Samuel Division of Medicinal Chemistry and Pharmacognosy College of Pharmacy, The Ohio State University, 43210, Columbus, Ohio, USA aut Mao Yicheng Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut Cho Youngah Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut Lee L. NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, 43210, Columbus, Ohio, USA aut Lee Robert Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut Lin Young Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3256-3264 0724-8741 28:12<3256 2011 28 11095 https://doi.org/10.1007/s11095-011-0498-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0498-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Li Hong Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Piao Longzhu Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Xu Pingping Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Ye Weiping Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Zhong Saiyi Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Lin Shu-Hong Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Kulp Samuel Division of Medicinal Chemistry and Pharmacognosy College of Pharmacy, The Ohio State University, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Mao Yicheng Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Cho Youngah Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Lee L. NSF Nanoscale Science and Engineering Center (NSEC), The Ohio State University, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Lee Robert Division of Pharmaceutics, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 700 1- Lin Young Laboratory of Reproductive and Molecular Endocrinology College of Veterinary Medicine, The Ohio State University, 1925 Coffey Road, 43210, Columbus, Ohio, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3256-3264 0724-8741 28:12<3256 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer