title: Chain elongation analog of resveratrol as potent cancer chemoprevention agent.
abstract: Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism.
authors.affiliation: College of Laboratory Medicine, Hebei North University, 11 Diamond Street South, Zhangjiakou, 075000, Hebei Province, People's Republic of China. kangyanfei172@163.com.
authors.forename: Yan-Fei
authors.initials: YF
authors.lastname: Kang
authors.affiliation: College of Laboratory Medicine, Hebei North University, 11 Diamond Street South, Zhangjiakou, 075000, Hebei Province, People's Republic of China.
authors.forename: Hai-Xia
authors.initials: HX
authors.lastname: Qiao
authors.affiliation: College of Agriculture and Forestry Science and Technology, Hebei North University, Zhangjiakou, 075000, Hebei, China.
authors.forename: Long-Zuo
authors.initials: LZ
authors.lastname: Xin
authors.affiliation: College of Laboratory Medicine, Hebei North University, 11 Diamond Street South, Zhangjiakou, 075000, Hebei Province, People's Republic of China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Ge
mesh_terms: D016588:Anticarcinogenic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D053453:Caspase 9 / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D010636:Phenols / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011090:Polyenes / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013267:Stilbenes / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000819:agonists / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D009363:Neoplasm Proteins; D010636:Phenols; D011090:Polyenes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Cell apoptosis; Cell cycle arrest; Chemopreventive agent; Isoprene unit; Resveratrol