Most Cited Article – Exposure of Hepatocellular Carcinoma Cells to Ankaferd Blood Stopper® Alters Cell Death Signaling Networks Confirmed by Oncoproteomic and Genomic Profiling Studies

Author(s):Merve NenniSelin ÖncülAyşe ErcanMustafa Çelebierİncilay Süslü* and İbrahim Celalettin Haznedaroğlu

Volume 7, Issue 2, 2021

Published on: 17 January, 2020

Page: [246 – 258]

Pages: 13

DOI: 10.2174/2215083806666200117093815


Background: Ankaferd Blood Stopper® is a commercially available herbal extract with potent blood-stopping property and is clinically used to treat immediate dental, dermal, external and internal bleeding. Its possible anti-neoplastic effect or whether it ingenerates drug resistance in cells has not been previously scrutinized.

Objective: In the present study, HEPG2 hepatocellular carcinoma cell line was exposed to clinically used dose (8 μL/mL) of the blood stopper for 24 h and the behavioral changes were investigated on both proteomic and genomic levels.

Methods: Cell culture experiments were performed by using Ankaferd® application in HEPG2 cell line. Cytotoxic activity experiments with MTT, oncoproteomic studies with 2-D gel electrophoresis, genomic studies were performed with RT-PCR.

Results: It was seen that the agent did not significantly inhibit cell viability subsequent to 24 h of the treatment meanwhile, it clearly deducted cell viability after 72 h. Although reduction of HEPG2 cell proliferation was not witnessed as a response to 24 h of treatment with Ankaferd®, genomic and oncoproteomic analysis demonstrated diversification.

Conclusion: It was established that protein processing networks in endoplasmic reticulum which regulate protein folding, relocation and degradation were effected. Additionally, it was proved that along with the elongation of the exposure period, mitochondrial apoptotic pathway may be activated due to hnRNP F-p53 interaction. Given to the fact that the agent did not cause P-glycoprotein-dependent drug resistance unlike many clinically used chemotherapeutic agents, it can also be considered for combination treatment. Overall, these findings suggest that Ankaferd® offers a novel promising approach against hepatocellular carcinoma which needs further investigation. Read now:

Most Cited Article – The Evaluation of Safety Property and Apoptotic Efficacy of α-L-Guluronic Acid (G2013), as a Novel NSAID, Under In Vitro Examination on L929 and Hepatocellular Carcinoma Cell Lines

Author(s):Shahrzad HassaniJalil Tavakol AfshariFahimeh Jafarnezhad-Ansariha and Abbas Mirshafiey*

Volume 15, Issue 1, 2021

Published on: 13 January, 2022

Page: [9 – 15]Pages: 7

DOI: 10.2174/2772434416666210909111912


Background: Many investigations have expanded this concept that liver chronic inflammation has an essential role in persistent cell damages along with altering the liver microenvironment leading to fibrosis, cirrhosis, and finally, hepatocellular carcinoma (HCC). To reduce inflammation and relieve symptoms, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are commonly used; however, their long-term usage can lead to severe adverse events on vital organs like the liver. Interestingly, the α-L-Guluronic Acid (G2013), as a novel NSAID with immunomodulatory properties, has shown the inhibitory effects on inflammation and metastasis in experimental models.

Objective: This study was conducted to determine the effects of G2013 on cytotoxicity and induction of apoptosis, as a new therapeutic target for cancer therapy, in the HepG2 cell line and the mouse fibroblast cell line L929, as a control.

Methods: MTT assay and flow cytometry method were carried out using the different concentrations of G2013 (5, 15, 25, 50, 100, 200 and 400 μg/ml) in 3 distinct incubation times.

Results: Our data showed that treatment of HepG2 cells with high concentration (400μg/mL) of G2013 could effectively cause a decrease in cell viability, so that they were statistically different after 72 hours compared to other concentrations (5 to 200 μg/ml) (p<0.05 and p<0.01, respectively). Moreover, the proportion of apoptosis of HepG2 cells at the dose of 200μg/mL considerably increased, suggesting that the induction of apoptosis by G2013 in HepG2 cells is dose- and time-dependent, which could promote its anticancer properties.

Conclusion: The present study revealed that G2013 could induce apoptosis in the liver cancer model. Therefore, based on these findings, G2013 might be considered as a therapeutic option in cancer therapy. Read now:

Testimonial | Read what our Authors have to say about publishing in our Journal – By Dr. Sherien M. El-Daly


Sherien M. El-Daly


Journal Name: Anti-Cancer Agents In Medicinal Chemistry


Contributed Article: Synergistic Effect of Α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells

Editors Choice Article | EH-42: A Novel Small Molecule Induces Apoptosis and Inhibits Migration and Invasion of Human Hepatoma Cells through Suppressing STAT3 Signaling Pathway

Journal Name: Current Cancer Drug Targets

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:

Animated Abstracts for Articles | Preliminary Study on the Mechanism of Carvacrol Regulating Hepatocellular Carcinoma Based on Network Pharmacology

Preliminary Study on the Mechanism of Carvacrol Regulating Hepatocellular Carcinoma Based on Network Pharmacology

Journal: Letters in Drug Design & Discovery 

AuthorPro.Lidao Bao

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:

MOST ACCESSED ARTICLE – Diagnostic Imaging of Hepatocellular Carcinoma – Current Medical Imaging Reviews

Journal: Current Medical Imaging Reviews

Author(s): Tomasz K. Nowicki*, Karolina Markiet, Edyta Szurowska

Graphical Abstract:



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.

Lastly, the EASL-EORTC guidelines are compared with the guidelines of the American Association for the Study of Liver Diseases and the Japan Society of Hepatology. Also LI-RADS and the Barcelona Clinic Liver Cancer classification are mentioned.
In the near future, due to the ongoing advances in imaging a revision of the guidelines may be expected.


Highlighted Article – Association of IL-12 B Gene Polymorphism with Staging of Liver Disease in Chronic HCV Patients – Infectious Disorders – Drug Targets

iddt-Articles_17-3-nadia elwan

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EurekAlert! – Towards the goal of precision therapy in hepatocellular carcinoma

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

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