The role of thioredoxin reductase and glutathione reductase in plumbagin-induced, reactive oxygen species-mediated apoptosis in cancer cell lines

European Journal of Pharmacology
Geun Hye HwangMin Young Lee

Abstract

Plumbagin is a secondary metabolite that was first identified in the Plumbago genus of plants. It is a naphthoquinone compound with anti-atherosclerosis, anticancer, anti-inflammatory, antimicrobial, contraceptive, cardiotonic, immunosuppressive, and neuroprotective activities. However, the mechanisms of plumbagin's activities are largely unknown. In this study, we examined the effect of plumbagin on HepG2 hepatocellular carcinoma cells as well as LLC lung cancer cells, SiHa cervical carcinoma cells. Plumbagin significantly decreased HepG2 cell viability in a dose-dependent manner. Additionally, treatment with plumbagin significantly increased the Bax/Bcl-2 ratio and caspase-3/7 activity. Using the similarity ensemble approach (SEA)-a state-of-the-art cheminformatic technique-we identified two previously unknown cellular targets of plumbagin: thioredoxin reductase (TrxR) and glutathione reductase (GR). This was then confirmed using protein- and cell-based assays. We found that plumbagin was directly reduced by TrxR, and that this reduction was inhibited by the TrxR inhibitor, sodium aurothiomalate (ATM). Plumbagin also decreased the activity of GR. Plumbagin, and the GR inhibitor sodium arsenite all increased intracellular reac...Continue Reading

References

Jan 16, 1995·FEBS Letters·S ToyokuniH Hiai
Apr 28, 2004·Free Radical Biology & Medicine·Ken ItohMasayuki Yamamoto
Jul 21, 2004·Molecular Carcinogenesis·Priya SrinivasGopal Srinivas
Dec 17, 2004·Toxicological Sciences : an Official Journal of the Society of Toxicology·V M RodríguezM E Gonsebatt
Jan 11, 2005·The Journal of Pharmacy and Pharmacology·Yaxian DingChung-Ho Chang
Sep 1, 2005·Apoptosis : an International Journal on Programmed Cell Death·N Hail
Feb 3, 2006·Diabetes/metabolism Research and Reviews·Ludovica PiconiAntonio Ceriello
Jun 27, 2006·Investigative Ophthalmology & Visual Science·Anne HannekenPamela Maher
Oct 5, 2006·Anti-cancer Agents in Medicinal Chemistry·Rajeshwar P Verma
Feb 9, 2007·Nature Biotechnology·Michael J KeiserBrian K Shoichet
Feb 27, 2007·Oncogene·J M Adams, S Cory
Dec 27, 2007·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M Gordaliza
Apr 21, 2009·International Immunopharmacology·Rahul CheckerT B Poduval
Dec 24, 2009·Journal of Neurochemistry·Tae Gen SonMark P Mattson
Jun 2, 2011·Nature Reviews. Drug Discovery·Grant R DrummondChristopher G Sobey
Jul 26, 2011·Biochimica Et Biophysica Acta·Stefanie Prast-NielsenDavid L Williams
Oct 13, 2012·Medicinal Research Reviews·Subhash PadhyeFazlul H Sarkar
Mar 30, 2013·Biochemical and Biophysical Research Communications·Tae Gen SonSimonetta Camandola
May 22, 2013·Mutation Research·Sanjeev KumarArun Sharma
Nov 12, 2013·Nucleic Acids Research·A Patrícia BentoJohn P Overington
Jan 11, 2014·Biochemical Pharmacology·Lokesh GambhirSantosh K Sandur
May 16, 2014·Metallomics : Integrated Biometal Science·Zuandi LuoTianfeng Chen

❮ Previous
Next ❯

Citations

Oct 30, 2016·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Taylor RohMyeong Jin Nam
Jun 6, 2018·Frontiers in Chemistry·Hongbin HuangZunnan Huang
Aug 8, 2019·Cancer Cell International·Carolina Escardó PereyraFloriano Paes Silva-Jr
Dec 12, 2018·Journal of Cellular Biochemistry·Yuning LinYanfei Wei
Oct 30, 2020·Antioxidants & Redox Signaling·Junmin ZhangJianguo Fang
Apr 2, 2021·The Journal of Pharmacy and Pharmacology·Danfeng XueJiaxuan Qiu

❮ Previous
Next ❯

Related Concepts

Related Feeds

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.

Apoptotic Caspases

Apoptotic caspases belong to the protease enzyme family and are known to play an essential role in inflammation and programmed cell death. Here is the latest research.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

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

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.