title: Delivery of ursolic acid (UA) in polymeric nanoparticles effectively promotes the apoptosis of gastric cancer cells through enhanced inhibition of cyclooxygenase 2 (COX-2).
abstract: It has been demonstrated that ursolic acid (UA) could effectively induces apoptosis of cancer cells by inhibiting the expression of cyclooxygenase 2 (COX-2), which constitutively expresses in gastric cancer. However, the hydrophobicity of UA increases the difficulty in its potential clinical application, which raises the possibility for its application as a novel model drug in nanoparticle-based delivery system. UA-loaded nanoparticles (UA-NPs) were prepared by a nano-precipitation method using amphilic methoxy poly(ethylene glycol)-polycaprolactone (mPEG-PCL) block copolymers as drug carriers. UA was effectively transported into SGC7901 cells by nanoparticles and localized around the nuclei in the cytoplasms. The in vitro cytotoxicity and apoptosis test indicated that UA-NPs significantly elicited more cell death at almost equivalent dose and corresponding incubation time. Moreover, UA-NPs led to more cell apoptosis through stronger inhibition of COX-2 and activation of caspase 3. The most powerful evidence from this report is that the significant differences between the cytotoxicity of free UA and UA-NPs are closely related to the expression levels of COX-2 and caspase-3, which demonstrates the superiority of UA-NPs over free UA through penetrating cell membrane. Therefore, the study offer an effective way to improve the anticancer efficiency of UA through nano-drug delivery system.
authors.affiliation: Department of Geriartric Gerontology, The First Affiliated Hospital to Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Ding
authors.forename: Huae
authors.initials: H
authors.lastname: Xu
authors.forename: Xinzheng
authors.initials: X
authors.lastname: Dai
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Hou
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Sun
authors.forename: Weihao
authors.initials: W
authors.lastname: Sun
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D014315:Triterpenes / Q000008:administration & dosage* / Q000494:pharmacology; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053148:Caspase 3; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D011091:Polyesters; D011092:Polyethylene Glycols; D014315:Triterpenes; D000097245:Ursolic Acid; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone)