title: A novel water-soluble gossypol derivative increases chemotherapeutic sensitivity and promotes growth inhibition in colon cancer.
abstract: 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.
authors.affiliation: Laboratory 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), Shanghai 200025, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yan
authors.forename: Xing-Xin
authors.initials: XX
authors.lastname: Cao
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Jiang
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhao
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Wang
authors.forename: Yi-Hui
authors.initials: YH
authors.lastname: Lin
authors.forename: Qiao-Ling
authors.initials: QL
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.forename: Biao
authors.initials: B
authors.lastname: Jiang
authors.forename: Fang
authors.initials: F
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006072:Gossypol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009368:Neoplasm Transplantation; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014867:Water
chemical_list: C551940:6-aminopenicillanic acid gossypolone; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014867:Water; D010396:Penicillamine; D006072:Gossypol; D005472:Fluorouracil