Combined treatment with sorafenib and silibinin synergistically targets both HCC cells and cancer stem cells by enhanced inhibition of the phosphorylation of STAT3/ERK/AKT

European Journal of Pharmacology
Jie MaoYong Yang

Abstract

Silibinin, a nontoxic bioactive component in milk thistle, is used as a liver-protective drug in the clinic mainly because of its antioxidant and anti-inflammation activities. In this study, we studied the cytotoxic effects of silibinin combined with sorafenib on hepatocellular carcinoma (HCC). The results indicated that silibinin combined with sorafenib potently inhibited the proliferation of various HCC cells and induced significant apoptosis. In an HCC subcutaneous transplantation tumor model, the combination of silibinin and sorafenib significantly suppressed tumor growth compared with monotherapy. As determined by fluorescence staining and Western blots, the combination of the two drugs inhibited the phosphorylation of RAC-alpha serine/threonine-protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) together with the expression of antiapoptotic proteins including myeloid leukemia cell differentiation protein Mcl-1 (Mcl-1) and apoptosis regulator Bcl-2 (Bcl-2), resulting in the death of cancer cells. We also found that the combination inhibited the formation and self-renewal of HCC stem cells by down-regulating the expression of stemness-related proteins, such as Homeobox protein NANOG (Nanog) a...Continue Reading

References

Feb 18, 2004·Current Cancer Drug Targets·Rana P Singh, Rajesh Agarwal
Aug 9, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Rana P Singh, Rajesh Agarwal
Apr 26, 2006·Molecular Carcinogenesis·Rana P Singh, Rajesh Agarwal
Oct 4, 2006·Nature Reviews. Drug Discovery·Scott WilhelmSusan Kelley
Nov 2, 2006·Investigational New Drugs·Thomas W FlaigL Michael Glodé
Nov 22, 2007·Expert Opinion on Drug Metabolism & Toxicology·Robert O'ConnorLorraine O'Driscoll
May 13, 2008·Cancer Letters·Kumaraguruparan Ramasamy, Rajesh Agarwal
Jul 25, 2008·The New England Journal of Medicine·Josep M LlovetUNKNOWN SHARP Investigators Study Group
Nov 21, 2008·Leukemia & Lymphoma·Ting-Chao Chou
Sep 26, 2009·Biochemical and Biophysical Research Communications·Hui-Jung JungWon-Ki Baek
Jan 6, 2010·Expert Opinion on Investigational Drugs·Lei LiDalin He
Mar 11, 2010·Cancer Research·Subapriya RajamanickamRajesh Agarwal
Aug 18, 2010·Cancer Metastasis Reviews·Gagan Deep, Rajesh Agarwal
Jun 21, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hasan KorkayaMax S Wicha
Aug 9, 2012·European Journal of Medicinal Chemistry·Kuen-Feng ChenChung-Wai Shiau
Jun 14, 2013·Journal of Clinical Gastroenterology·Jean K Lee, Ghassan K Abou-Alfa
Feb 18, 2014·Gut·Jordi BruixVincenzo Mazzaferro
Mar 6, 2015·World Journal of Gastroenterology : WJG·Jung Gil ParkHye Won Lee
Aug 1, 2015·World Journal of Gastroenterology : WJG·Alexander SchlachtermanRoniel Cabrera
Aug 26, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Tarek Kamal MotawiHebatullah Samy Helmy
Jan 26, 2016·CA: a Cancer Journal for Clinicians·Wanqing ChenJie He
Jun 2, 2016·Acta histochemica·Miroslava JuríkováIvan Varga

❮ Previous
Next ❯

Citations

Jun 21, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Fujia LinCaiwen Ou
Feb 25, 2020·Current Topics in Medicinal Chemistry·Muhammad Shoaib Ali GillNafees Ahemad
Jan 6, 2019·Pharmaceuticals·Barbara Guerra, Olaf-Georg Issinger
Jun 11, 2020·Therapeutic Advances in Medical Oncology·Guanghan FanXiao Xu
Jan 10, 2021·Life Sciences·Md Abdul AzizZhang Hongjie
Mar 7, 2021·International Journal of Molecular Sciences·Mai-Huong Thi NgoYen-Hua Huang
Jan 25, 2020·Anti-cancer Agents in Medicinal Chemistry·Diana S AntalCristina Dehelean
May 5, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Olaf-Georg Issinger, Barbara Guerra
May 23, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shufang ZhengWeiwei Hu
May 30, 2021·Medical Oncology·Jacqueline R LimAnn H Kwan
Jul 31, 2021·Bioorganic Chemistry·Vikram Jeet SinghPooja A Chawla
Jul 28, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Agnieszka KarbownikEdyta Szałek
Oct 26, 2020·Biochimica Et Biophysica Acta. Molecular Cell Research·Jiaojiao ZhengXiaojuan Du
Jan 13, 2022·Journal of Evidence-based Integrative Medicine·Tomas Koltai, Larry Fliegel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.