title: Synthesis and biological analysis of a new curcumin analogue for enhanced anti-tumor activity in HepG 2 cells.
abstract: The aim of the present study was to investigate the apoptosis of human hepatocellular carcinoma cell line HepG 2 induced by a new curcumin analogue, GL63. HepG 2 cells were treated with increasing doses of GL63 and curcumin for 48 h. The proliferation of cells was detected with MTT. The apoptosis were examined by flow cytometry. The caspase-3 activity was detected by western blotting. ER calcium stores were assessed by the fluorescent calcium indicator fura-2/AM. The protein expression of ER stress pathway, GRP78, XBP-1, ATF-4 and CHOP were examined with western blotting. Growth inhibitory effect was observed for treatment with GL63 in a dose-dependent manner and with more potential than curcumin. GL63 at 20 microM induced significant apoptosis in HepG 2 cells. Furthermore, GL63 induced the ER stress response, up-regulation of CHOP, XBP-1, ATF-4 and GRP78 expression in a dose-dependent, while curcumin had no effect on ER stress. These results suggest that GL63 has more potent anti-tumor activity than curcumin, which is associated with activation of ER stress and induction of apoptosis in HepG 2 cells.
authors.affiliation: Key Laboratory of Biotechnology Pharmaceutical Engineering, school of pharmaceutical science, Wenzhou Medical College, Wenzhou 325035, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chu
authors.forename: Keqiong
authors.initials: K
authors.lastname: Hu
authors.forename: Jin
authors.initials: J
authors.lastname: Wan
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.forename: Chengxi
authors.initials: C
authors.lastname: Jiang
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001969:Bromobenzenes / Q000138:chemical synthesis / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D005434:Flow Cytometry; D006360:Heat-Shock Proteins / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D010422:Pentanones / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D000071701:Regulatory Factor X Transcription Factors; D013312:Stress, Physiological / Q000187:drug effects; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1
chemical_list: C550703:1,5-bis(2-bromophenyl)penta-1,4-dien-3-one; C497109:ATF4 protein, human; D000972:Antineoplastic Agents, Phytogenic; D001969:Bromobenzenes; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010422:Pentanones; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605545:Xbp1 protein, rat; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; C505407:CASP3 protein, human; D053148:Caspase 3; D003474:Curcumin; D002118:Calcium