Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress-Ca2+-mitochondria dependent pathway

摘要: // Jing Zhang 1, * , Yang Wang Ye Zhou 1 and Qing-Yu He Key Laboratory of Functional Protein Research Guangdong Higher Education Institutes, Institute Life Health Engineering, College Science Technology, Jinan University, Guangzhou 510632, China These authors contributed equally to this work Correspondence to: He, email: tqyhe@jnu.edu.cn Keywords: jolkinolide B, iTRAQ proteomics, ROS, ER stress, Ca 2+ Received: May 13, 2017      Accepted: July 26, Published: August 09, 2017 ABSTRACT Colorectal carcinoma (CRC) remains one the leading causes death in cancer-related diseases. In study, we aimed investigate anticancer effect Jolkinolide B (JB), a bioactive diterpenoid component isolated from dried roots Euphorbia fischeriana Steud, on CRC cells its underlying mechanisms. We found that JB suppressed cell viability colony formation cells, HT29 SW620. Annexin V/PI assay revealed induced apoptosis which was further confirmed by increased expression cleaved-caspase3 cleaved-PARP. iTRAQ-based quantitative proteomics performed identify JB-regulated proteins cells. Gene Ontology (GO) analysis these were mainly involved stress response, evidenced marker proteins, HSP90, Bip PDI. Moreover, provoked generation reactive oxygen species (ROS), inhibition ROS with N-acetyl L-cysteine could reverse JB-induced apoptosis. Confocal microscopy flow cytometry showed treatment enhanced intracellular mitochondrial level JC-1 loss membrane potential after treatment. The uptake depolarization can be blocked Ruthenium Red (RuRed), an inhibitor uniporter. Taken together, demonstrated exerts stress-Ca -mitochondria signaling, suggesting promising chemotherapeutic for CRC.