title: Antitumor and apoptosis-promoting properties of emodin, an anthraquinone derivative from Rheum officinale Baill, against pancreatic cancer in mice via inhibition of Akt activation.
abstract: Pancreatic adenocarcinoma is one of the most common malignancies worldwide. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. However, gemcitabine can induce activation of Akt and nuclear factor-κB (NF-κB), which is associated with its chemoresistance. It has been reported that gemcitabine combination therapies result in improved survival outcomes in pancreatic cancer. Therefore, agents that can either enhance the effects of gemcitabine or overcome chemoresistance to the drug are needed for the treatment of pancreatic cancer. Emodin is an active component of Chinese medicinal herbs and can inhibit the activation of Akt and NF-κB. In this study, we investigated whether emodin could enhance the anticancer effect of gemcitabine on pancreatic cancer in vivo. We demonstrated that treatment of gemcitabine combined with emodin efficiently suppressed tumor growth in mice inoculated with pancreatic tumor cells. This treatment paradigm promoted apoptotic cell death and mitochondrial fragmentation. Furthermore, it reduced phosphorylated-Akt (p-Akt) level, NF-κB activation and Bcl-2/Bax ratio, increased caspase-9 and -3 activation, Cytochrome C (CytC) release occurred in combination therapy. Collectively, emodin enhanced the activity of gemcitabine in tumor growth suppression via inhibition of Akt and NF-κB activation, thus promoting the mitochondrial-dependent apoptotic pathway. Therefore, our findings may provide new insights into understanding the pharmacological regulation of emodin on gemcitabine-mediated proapoptosis in pancreatic cancer and may aid in the design of new therapeutic strategies for the intervention of human pancreatic cancers.
authors.affiliation: Department of Hepato-biliary-pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, No. 109, West Xue-yuan Road, Wenzhou 325027, P.R. China.
authors.forename: Wei-Tian
authors.initials: WT
authors.lastname: Wei
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Zhong-Lin
authors.initials: ZL
authors.lastname: Ni
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Liu
authors.forename: Hong-Fei
authors.initials: HF
authors.lastname: Tong
authors.forename: Ling
authors.initials: L
authors.lastname: Fan
authors.forename: An
authors.initials: A
authors.lastname: Liu
authors.forename: Mai-Xuan
authors.initials: MX
authors.lastname: Qiu
authors.forename: Dian-Lei
authors.initials: DL
authors.lastname: Liu
authors.forename: Hong-Chun
authors.initials: HC
authors.lastname: Guo
authors.forename: Zhao-Hong
authors.initials: ZH
authors.lastname: Wang
authors.forename: Sheng-Zhang
authors.initials: SZ
authors.lastname: Lin
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D004642:Emodin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012250:Rheum / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D004642:Emodin