title: A new curcumin analogue exhibits enhanced antitumor activity in nasopharyngeal carcinoma.
abstract: The aim of the present study was to evaluate the antitumor effects of the curcumin analogue GL63 on radioresistant nasopharyngeal carcinoma (NPC) CNE2R cells and parental CNE2 cells. The cell viability and proliferation of NPC cells were detected by MTT assay and colony formation assay. The suppressive effect on tumor growth was examined using in vivo subcutaneously inoculated NPC tumor models using nude mice. The cell cycle distribution was detected using flow cytometry. Apoptosis was examined by Hoechst 33342 and Annexin V/PI staining assay. The protein expression of endoplasmic reticulum (ER) stress pathway markers, XBP-1, ATF-4 and CHOP, were examined by western blotting. A growth inhibitory effect was observed following treatment with GL63 in a dose-dependent manner and was more potent when compared to curcumin. GL63 at 5 µM induced significant G2/M arrest and apoptosis in NPC. The tumor-suppressive activity of GL63 in NPC xenograft models was more potent when compared to curcumin. Furthermore, GL63 induced an ER stress response, upregulation of CHOP, XBP-1 and ATF-4 expression, while the same concentration of curcumin had no effect on ER stress. These results suggest that GL63 has more potent antitumor activity than curcumin, which is associated with activation of ER stress, induction of G2/M arrest and apoptosis in NPC cells.
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Yunbao
authors.initials: Y
authors.lastname: Pan
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.forename: Mengyao
authors.initials: M
authors.lastname: Wang
authors.forename: Dujuan
authors.initials: D
authors.lastname: Wang
authors.forename: Sumei
authors.initials: S
authors.lastname: Wang
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
mesh_terms: D051701:Activating Transcription Factor 4 / Q000096:biosynthesis; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001969:Bromobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy*; D010422:Pentanones / Q000494:pharmacology* / Q000627:therapeutic use; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D000071717:X-Box Binding Protein 1; D023041:Xenograft Model Antitumor Assays
chemical_list: C550703:1,5-bis(2-bromophenyl)penta-1,4-dien-3-one; C497109:ATF4 protein, human; D000970:Antineoplastic Agents; D001969:Bromobenzenes; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D010422:Pentanones; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C000605544:Xbp1 protein, mouse; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D003474:Curcumin