title: Curcumin enhances the antitumor effect of ABT-737 via activation of the ROS-ASK1-JNK pathway in hepatocellular carcinoma cells.
abstract: At present, the therapeutic treatment strategies for patients with hepatocellular carcinoma (HCC) remain unsatisfactory, and novel methods are urgently required to treat this disease. Members of the B cell lymphoma (Bcl)-2 family are anti‑apoptotic proteins, which are commonly expressed at high levels in certain HCC tissues and positively correlate with the treatment resistance of patients with HCC. ABT-737, an inhibitor of Bcl-2 anti-apoptotic proteins, has been demonstrated to exhibit potent antitumor effects in several types of tumor, including HCC. However, treatment with ABT-737 alone also activates certain pro-survival signaling pathways, which attenuate the antitumor validity of ABT-737. Curcumin, which is obtained from Curcuma longa, is also an antitumor potentiator in multiple types of cancer. In the present study, the synergistic effect of curcumin and ABT-737 on HCC cells was investigated for the first time, to the best of our knowledge. It was found that curcumin markedly enhanced the antitumor effects of ABT-737 on HepG2 cells, which was partially dependent on the induction of apoptosis, according to western blot analysis and flow cytometric apoptosis analysis. In addition, the sustained activation of the ROS-ASK1-c-Jun N-terminal kinase pathway may be an important mediator of the synergistic effect of curcumin and ABT-737. Collectively, these results indicated that the combination of curcumin and ABT-737 can efficaciously induce the death of HCC cells, and may offer a potential treatment strategy for patients with HCC.
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Ruinian
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Oncology, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: You
authors.affiliation: Department of Oncology, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.affiliation: Department of Oncology, Dongguan People's Hospital, Dongguan, Guangdong 523000, P.R. China.
authors.forename: Shunhuan
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Oncology, The Second People's Hospital of Shenzhen, Shenzhen, Guangdong 518035, P.R. China.
authors.forename: Aixue
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, Affiliated Cancer Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510095, P.R. China.
authors.forename: Huidong
authors.initials: H
authors.lastname: Long
authors.affiliation: Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P.R. China.
authors.forename: Senming
authors.initials: S
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000096:biosynthesis* / Q000235:genetics; D048848:MAP Kinase Kinase Kinase 5 / Q000096:biosynthesis* / Q000235:genetics; D009596:Nitrophenols / Q000008:administration & dosage; D010879:Piperazines / Q000008:administration & dosage; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D015398:Signal Transduction; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: C501332:ABT-737; D001713:Biphenyl Compounds; D009596:Nitrophenols; D010879:Piperazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013449:Sulfonamides; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human; D048670:MAP Kinase Kinase 4; D003474:Curcumin