Journal Name: Anti-Cancer Agents In Medicinal Chemistry
Author(s): Qi-Zhe Gong, Di Xiao, Gui-Yi Gong, Jian Xu, Xiao-Dong Wen*, Feng Feng*, Wei Qu*.
Background: Since signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in hepatocellular carcinoma (HCC) and plays a key role in this tumor progression. Inhibition of the STAT3 signaling pathway has been considered as an effective therapeutic strategy for suppressing HCC development.
Objective: In this study, we investigated the anti-cancer effects of EH-42 on HCC cells and tried to explain the underlying mechanism.
Methods: MTT assay, colon formation assay and AnnexinV-FITC/PI double-staining assay were performed to assess the effects of EH-42 on cell growth and survival. Wound healing assay and transwell invasion assay were performed to assess the effects of EH-42 on cell migration and invasion. Western blotting assay was performed to analyze the effects of EH-42 on relative proteins.
Results: According to the MTT assay, colon formation assay and AnnexinV-FITC/PI doublestaining assay, EH-42 could suppress the growth and induce apoptosis of HCC cells in a dosedependent manner. Further western blotting assay showed that the inhibitory effects of EH-42 on cell growth and survival were caused by activating caspase 3/9, suppressing the phospho-STAT3 (Tyr 705) and downregulating anti-apoptotic proteins like Bcl-2/Bcl-xL. Moreover, migration and invasion abilities of HCC cells were also inhibited by EH-42 in the wound healing assay and transwell invasion assay. The potential mechanism was that EH-42 could inhibit HCC metastasis via reversing epithelial-mesenchymal transition and downregulating the secretion of MMPs.
Conclusion: Taken together, these findings suggested that EH-42 could be a potential therapeutic agent for HCC treatment. To read out more, please visit: http://www.eurekaselect.com/168569/article
Objective: To predict and analyze the target of anti-Hepatocellular Carcinoma(HCC) in the active constituents of Safflower by using network pharmacology.
Methods: The active compounds of safflower were collected by TCMSP, TCM-PTD database and literature mining methods. The targets of active compounds were predicted by Swiss Target Prediction server, and the target of anti-HCC drugs was collected by DisGeNET database. The target was subjected to an alignment analysis to screen out the Carvacrol, a target of safflower against HCC. The mouse HCC model was established and treated with Carvacrol. The anti-HCC target DAPK1 and PPP2R2A were verified by Western blot and co-immunoprecipitation.
Results: A total of 21 safflower active ingredients were predicted. Carvacrol was identified as a possible active ingredient according to the five principles of drug-like medicine. According to Carvacrol’s possible targets and possible targets of HCC, three co-targets were identified, including cancer-related are DAPK1 and PPP2R2A. After 20 weeks of Carvacrol treated , Carvacrol group significantly increased on DAPK1 levels and decreased PPP2R2A levels in the model mice by Western blot. Immunoprecipitation confirmed the endogenous interaction between DAPK1 and PPP2R2A.
Conclusion: Safflower can regulate the development of HCC through its active component Carvacrol, which can affect the expression of DAPK1 and PPP2R2A proteins, and the endogenous interactions of DAPK1 and PPP2R2A proteins. To read out full article, please visit: http://www.eurekaselect.com/172163/article
Journal: Current Medical Imaging Reviews
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which develops mostly in the setting of chronic liver disease. European Association for the Study of the Liver (EASL) and European Organization for Research and Treatment of Cancer (EORTC) prepared guidelines for screening, follow-up and diagnosis of HCC to facilitate decision making and optimize both diagnostic and therapeutic protocols.
The review briefly describes etiology, epidemiology and histopathology of HCC and presents EASL-EORTC guidelines for surveillance and diagnosis of HCC. Target population and screening algorithm is presented in the surveillance section. Ultrasound imaging of HCC and the role of contrast enhanced ultrasound are described as well as the value of laboratory tests in screening. Further, radiological features of HCC in multiphase CT and dynamic contrast enhanced MRI and diagnostic criteria are presented. Additionally, the advantages of advanced techniques in MRI such as diffusion weighed imaging and the use of hepatocyte-specific contrast agents are discussed.
Hepatocellular carcinoma is a highly lethal disease, therefore effective and tolerable treatment is urgently needed.
Advances in understanding the molecular genetics of hepatocellular neoplasia have been made, and developing targeted therapeutics in combination with molecular tumor profiling may help accomplish the goal of precision treatment of patients with hepatocellular carcinoma (HCC).
In a recently published article, Dr. Nelson Yee and Dr. Eric Marks provide an updated review of the genetic abnormalities and mechanisms that drive carcinogenesis of HCC, and discuss the targeted therapeutics clinically investigated in patients with this disease.
The article is published in Current Cancer Drug Targets 2016; volume 16, issue 1, pages 53-70.
Eric I. Marks and Nelson S Yee.
Penn State Hershey Cancer Institute, 500 University Drive, Hershey, Pennsylvania, USA
Read more here: http://www.eurekalert.org/pub_releases/2016-03/bsp-ttg030716.php