8-Cetylcoptisine, a new coptisine derivative, induces mitochondria-dependent apoptosis and G0/G1 cell cycle arrest in human A549 cells. (1st February 2019)

• Record Type: Journal Article
• Authors: Han, Bing; Jiang, Pu; Xu, Heshan; Liu, Wuyang; Zhang, Jian; Wu, Siqi; Liu, Liangyu; Ma, Wenyu; Li, Xuegang; Ye, Xiaoli
• Is Part Of: Chemico-biological interactions. Volume 299(2019)
• Page Start: 27
• Page End: 36
• Publication Date: 2019-02-01
• Subjects: Coptisine derivative -- 8-Cetylcoptisine -- Lung cancer -- Apoptosis -- Cell cycle; Akt protein kinase B -- AO/EB acridine orange/ethidium bromide -- Bak Bcl-2 homologous antagonist/killer -- Bax Bcl-2-associated X protein -- Bcl-2 B-cell lymphoma 2 -- CCOP 8-cetylcoptisine -- CDKs cyclin dependent kinases -- COP coptisine -- DiOC6(3) 3, 3′-dihexyloxacarbocyanine iodide -- DMEM Dulbecco's Modified Eagle's Medium -- MMP mitochondrial membrane potential -- MOMP mitochondrial outer membrane permeabilization -- NSCLC non-small-cell lung cancer -- PARP poly ADP-ribose polymerase -- PI propidium iodide -- Pi3k phosphoinositide 3-kinase; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2018.11.005
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Lung cancer is the worldwide leading cause of cancer-related death. Here, we described the synthesis and the anticancer activity of a novel coptisine derivative 8-cetylcoptisine (CCOP) on lung carcinoma in vitro and in vivo . CCOP inhibited the cell viability of A549, BGC-823, MDA-MB-231, HCT-116 and HepG2 cell lines. In A549 cells, CCOP induced apoptosis, G0/G1 cell cycle arrest and decreased mitochondrial membrane potential (MMP) in a dose-dependent manner. Western blot analysis showed that CCOP increased the expression of Bcl-2-associated X protein (Bax), cleaved caspase 3 and 9, while decreased B-cell lymphoma 2 (Bcl-2), cyclins D and E, cyclin dependent kinases (CDKs) 2, 4 and 6, along with the inactivation of the upstream phosphoinositide 3-kinase (Pi3k)/protein kinase B (Akt) signaling. Further in vivo studies showed that CCOP (10 mg/kg) significantly delayed tumor growth in A549 xenograft nude mice, which is stronger than that of coptisine (100 mg/kg). These data suggested that CCOP could be a candidate for lung cancer therapy. Graphical abstract: Highlights: A new coptisine derivative 8-cetylcoptisine is synthesized and characterized. CCOP inhibits cell growth in A549 and other cancer cell lines. CCOP induces mitochondria-dependent apoptosis and G0/G1 arrest in A549 cells. CCOP exhibits better antitumor effect than COP in A549 xenograft nude mice.