Статья

A Novel Water-Soluble Gossypol Derivative Increases Chemotherapeutic Sensitivity and Promotes Growth Inhibition in Colon Cancer

Fei YanLaboratory of Targeted Cancer Therapy, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao-Tong University School of Medicine (SJTU-SM), No. 225, South Chongqing Road, Shanghai 200025, ChinaXingxin CaoCAS Key Laboratory of Synthetic Chemistry of Natural Substance, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, ChinaHaixia JiangCAS Key Laboratory of Synthetic Chemistry of Natural Substance, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, ChinaXiaolong ZhaoCAS Key Laboratory of Synthetic Chemistry of Natural Substance, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, ChinaJianyong WangLaboratory of Targeted Cancer Therapy, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao-Tong University School of Medicine (SJTU-SM), No. 225, South Chongqing Road, Shanghai 200025, ChinaYi-Hui LinLaboratory of Targeted Cancer Therapy, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao-Tong University School of Medicine (SJTU-SM), No. 225, South Chongqing Road, Shanghai 200025, ChinaQiaoling LiuLaboratory of Targeted Cancer Therapy, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao-Tong University School of Medicine (SJTU-SM), No. 225, South Chongqing Road, Shanghai 200025, ChinaChen ZhangCAS Key Laboratory of Synthetic Chemistry of Natural Substance, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, ChinaBiao JiangCAS Key Laboratory of Synthetic Chemistry of Natural Substance, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, ChinaFang GuoLaboratory of Targeted Cancer Therapy, Institute of Health Sciences, Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao-Tong University School of Medicine (SJTU-SM), No. 225, South Chongqing Road, Shanghai 200025, China

2010en

ABI

Аннотация

Compound 1 ((-)-gossypol) has been long known as a chemical anticancer agent. With its low water solubility and toxicity, it is not widely used as a commercial drug. To overcome these disadvantages, several novel derivatives of gossypol were designed, synthesized, and analyzed. One of the derivatives, compound 7 (6-aminopenicillanic acid sodium-gossypolone), was identified with great water solubility and anticancer property, suggested by inducing a dramatically decrease in Bcl-2 and Bcl-xL protein expression level found in vitro and growth inhibition of murine colon tumor in vivo. Furthermore, it was also recognized with less toxicity than compound 1 in vivo and significantly increased chemotherapeutic sensitivity against colon cancer in combination with traditional chemotherapeutic agent 5-fluorouracil. Therefore, it is concluded that compound 7 is superior to parent compound 1, and further preclinical studies of compound 7 is necessary for colon cancer therapy.

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Идентификаторы

DOI: 10.1021/jm1001698

Цитирования и источники

Цитирований: 3Использованных источников: 0

Показатели — AkademScholar