title: A supermolecular curcumin for enhanced antiproliferative and proapoptotic activities: molecular characteristics, computer modeling and in vivo pharmacokinetics.
abstract: The  supermolecular curcumin (SMCCM) exhibiting remarkably improved solubility and release characteristics was fabricated to increase the oral bioavailability in rat as well as the antiproliferative and proapoptotic activities of curcumin (CCM) against human lung adenocarcinoma cell A549. SMCCM was characterized by differential scanning calorimetry, Fourier transform infrared spectroscopy, morphology and structure, aqueous solubility, and release behavior in vitro. Computer modeling of the supermolecular structure was performed. The pharmacokinetics, antiproliferative and proapoptotic activities of SMCCM were evaluated. The mechanisms by which SMCCM inhibited proliferation and induced apoptosis were identified. The formation of SMCCM was testified and the supermolecular structure was studied by a computer modeling technique. Compared to free CCM, SMCCM with much higher aqueous solubility exhibited obviously enhanced release and more favorable pharmacokinetic profiles, and, furthermore, SMCCM showed higher anticancer efficacy, enhanced induction of G2/M-phase arrest and apoptosis in A549 cells, which might be involved with the increases in reactive oxygen species production and intracellular Ca(2+) accumulation, and a decrease in mitochondrial membrane potential. SMCCM remarkably enhanced not only the oral bioavailability but also the antiproliferative and proapoptotic activities of CCM along with improved solubility and release characteristics of CCM.
authors.affiliation: Department of Thoracic Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Qunyou
authors.initials: Q
authors.lastname: Tan
authors.forename: Jianyong
authors.initials: J
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Hu
authors.initials: H
authors.lastname: Mei
authors.forename: Chunjing
authors.initials: C
authors.lastname: Zhao
authors.forename: Jingqing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000166:cytology / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D003474:Curcumin; D002118:Calcium