title: Anti-cancer activity and potential mechanism of a novel aspirin derivative.
abstract: Aspirin has been used in the treatment and chemoprevention of many malignant cancers. The mechanism of its anti-cancer activity mainly involves the inhibition of cyclooxygenase-2 (COX-2). However, the application of aspirin is limited by the serious gastric mucosal damage that accompanies its usage. We have previously reported the preparation of a novel aspirin derivative that we named Ca-Asp, and showed that it causes less damage to gastric mucosa of rat and inhibits the expression of COX-2 to higher degree than Asp. However, the anti-cancer effect and mechanism of Ca-Asp was not demonstrated. In this study, the anti-cancer effect of Ca-Asp was investigated and compared with those of Asp and Hydroxyapatite (Hap) at the cell level. The results showed that treatment of SGC-7901 cells (human gastric cancer cell line) with 200-400μg/ml Ca-Asp resulted in significant reduction in cell viability, compared to treatment with either Asp or Hap, and at a higher concentration (500μg/ml). Subsequent investigation into the possible underlying mechanism showed that Ca-Asp induced apoptosis and caused cell cycle arrest at the G1 phase. Ca-Asp also up-regulated the levels of caspase-3 and p53, but down regulated the level of cyclin D1, NF-κB, COX-2 and PGE2. Furthermore, simultaneous treatment of SGC-7901 cells with Ca-Asp and exogenous PGE2reduced the anti-proliferative effect of Ca-Asp on the cells. Taken together, the results suggested that Ca-Asp might act as a potential anti-cancer drug, and that its suppression of PGE2production might constitute an important part of its anti-cancer activity.
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Ming
authors: M
authors: Zong
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Dan-Dan
authors: DD
authors: Fan
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Shan
authors: S
authors: Lin
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Yan-Ping
authors: YP
authors: Song
authors: School of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
authors: Ze-Yu
authors: ZY
authors: Wang
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Xiao-Liang
authors: XL
authors: Ma
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Wei-Hua
authors: WH
authors: Qiu
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Yu-Hua
authors: YH
authors: Bai
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China.
authors: Lei
authors: L
authors: Li
authors: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing 163319, China. Electronic address: lisen_116@163.com.
authors: Sen
authors: S
authors: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000737:chemistry* / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics; D015232:Dinoprostone / Q000096:biosynthesis; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D051546:Cyclooxygenase 2; D053148:Caspase 3; D015232:Dinoprostone; D001241:Aspirin
keywords: Anticancer effect; Aspirin (PubChem CID:2244); Aspirin-derivative; Ca-Asp; Caspase-3 (PubChem CID: 9840223); Cyclin D (PubChem CID: 171581456); Hydroxyapatite (PubChem CID: 14781); Mechanism; cyclooxygenase-2 (PubChem CID: 73416861)