title: Curcumin exerts antitumor effects in retinoblastoma cells by regulating the JNK and p38 MAPK pathways.
abstract: Curcumin, a naturally occurring polyphenolic compound present in turmeric (Curcuma longa), exerts antitumor effects in various types of malignancy. However, the precise mechanisms responsible for the effects of curcumin on retinoblastoma (RB) cells have not been fully explored. In the present study, the molecular mechanisms by which curcumin exerts its anticancer effects in RB Y79 cells were investigated. The results showed that curcumin reduced cell viability in Y79 cells. Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin-induced apoptosis of Y79 cells occurred through the activation of caspases-9/-3. Moreover, flow cytometric analysis showed that curcumin induced mitochondrial membrane potential (∆Ψm) collapse in Y79 cells. We also found that curcumin induced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). JNK and p38 MAPK inhibitors significantly suppressed curcumin‑induced activation of caspases-9/-3 and inhibited the apoptosis of Y79 cells. Taken together, our results suggest that curcumin induced the apoptosis of Y79 cells through the activation of JNK and p38 MAPK pathways. These findings provide a novel treatment strategy for human RB.
authors.affiliation: Department of Ophthalmology, Shandong Jiaotong Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Jingtao
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Ophthalmology, Shandong Jiaotong Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Shandong Jiaotong Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Shandong Jiaotong Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: Department of Otolaryngology, Shandong Jiaotong Hospital, Jinan, Shandong 250031, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D012175:Retinoblastoma / Q000378:metabolism / Q000473:pathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D053453:Caspase 9; D003474:Curcumin