Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
May-2018 Volume 41 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2018 Volume 41 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells

  • Authors:
    • Qiang Niu
    • Wei Zhao
    • Jin Wang
    • Chunming Li
    • Tao Yan
    • Wei Lv
    • Guojing Wang
    • Weihong Duan
    • Tao Zhang
    • Kunnan Wang
    • Dinghua Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary Surgery, Rocket Army General Hospital, Beijing 100088, P.R. China
    Copyright: © Niu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2601-2608
    |
    Published online on: February 16, 2018
       https://doi.org/10.3892/ijmm.2018.3499
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Chemotherapy is the best choice for the vast majority of hepatocellular carcinoma patients at late stage, but few effective chemotherapy drugs are available in clinic. Licochalcone A (LicA) is a new chemotherapy drug inducing apoptosis as Bcl-2 inhibitor, but few studies report on LicA‑induced autophagy. This study investigated the phenomenon and mechanisms of LicA-induced autophagy looking for a targeted combination drug. Human hepatocellular carcinoma cells (HCCs) were treated with LicA, to detect markers of autophagy and to investigate the mechanisms. In order to investigate the role of reactive oxygen species (ROS) in LicA‑induced autophagy, ROS, glutathione (GSH) and O2- were measured in LicA treated HCCs, and antioxidant N-Acetyl-L-cysteine (NAC) was cotreated with LicA in HCCs, then mechanisms of ROS-induced autophagy was investigated in LicA or LicA combined with NAC treated HCCs. Finally, the LicA-induced apoptosis was detected in LicA combined with NAC treated HCCs. We first report that LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, suppression of LicA-induced ROS through antioxidant NAC can enhance LicA-induced apoptosis, promoting the function of LicA killing HCCs. LicA can activate the ULK1/Atg13 complex which is upstream of autophagy, additionally, LicA also can promote ROS generation, ROS trigger the expression level of TSC1/2 complex, PRAS40, CTMP, PP2A, PDK1 and Rubicon change, these molecules are upstream of autophagy. In conclusion, LicA can induce autophagy through ULK1/Atg13 and ROS pathway in HCCs, LicA combined with NAC can enhance LicA-induced apoptosis. Our results may provide a novel design for clinical hepatocellular carcinoma therapy trials.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2015. CA Cancer J Clin. 65:5–29. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar

3 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Yo YT, Shieh GS, Hsu KF, Wu CL and Shiau AL: Licorice and licochalcone-A induce autophagy in LNCaP prostate cancer cells by suppression of Bcl-2 expression and the mTOR pathway. J Agric Food Chem. 57:8266–8273. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Lee CK, Son SH, Park KK, Park JH, Lim SS, Kim SH and Chung WY: Licochalcone A inhibits the growth of colon carcinoma and attenuates cisplatin-induced toxicity without a loss of chemotherapeutic efficacy in mice. Basic Clin Pharmacol Toxicol. 103:48–54. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Rafi MM, Rosen RT, Vassil A, Ho CT, Zhang H, Ghai G, Lambert G and DiPaola RS: Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid. Anticancer Res. 20:2653–2658. 2000.PubMed/NCBI

7 

Kwon HS, Park JH, Kim DH, Kim YH, Park JH, Shin HK and Kim JK: Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. J Mol Med (Berl). 86:1287–1295. 2008. View Article : Google Scholar

8 

Kim YH, Shin EK, Kim DH, Lee HH, Park JH and Kim JK: Antiangiogenic effect of licochalcone A. Biochem Pharmacol. 80:1152–1159. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Anding AL and Baehrecke EH: Autophagy in cell life and cell death. Curr Top Dev Biol. 114:67–91. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Sarbassov DD, Ali SM and Sabatini DM: Growing roles for the mTOR pathway. Curr Opin Cell Biol. 17:596–603. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Høyer-Hansen M and Jäättelä M: AMP-activated protein kinase: A universal regulator of autophagy. Autophagy. 3:381–383. 2007. View Article : Google Scholar

12 

Kazi AA and Lang CH: PRAS40 regulates protein synthesis and cell cycle in C2C12 myoblasts. Mol Med. 16:359–371. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Wong CP, Seki A, Horiguchi K, Shoji T, Arai T, Nugroho AE, Hirasawa Y, Sato F, Kaneda T and Morita H: Bisleuconothine a induces autophagosome formation by interfering with AKT-mTOR signaling pathway. J Nat Prod. 78:1656–1662. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Park J, Li Y, Kim SH, Yang KJ, Kong G, Shrestha R, Tran Q, Park KA, Jeon J, Hur GM, et al: New players in high fat diet-induced obesity: LETM1 and CTMP. Metabolism. 63:318–327. 2014. View Article : Google Scholar

15 

Yin X, Zhang N and Di W: Regulation of LC3-dependent protective autophagy in ovarian cancer cells by protein phosphatase 2A. Int J Gynecol Cancer. 23:630–641. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Gong FR, Wu MY, Shen M, Zhi Q, Xu ZK, Wang R, Wang WJ, Zong Y, Li ZL, Wu Y, et al: PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21. Oncotarget. 6:18469–18483. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Deng Q, Yu X, Xiao L, Hu Z, Luo X, Tao Y, Yang L, Liu X, Chen H, Ding Z, et al: Neoalbaconol induces energy depletion and multiple cell death in cancer cells by targeting PDK1-PI3-K/Akt signaling pathway. Cell Death Dis. 4:e8042013. View Article : Google Scholar : PubMed/NCBI

18 

Karlsson I, Zhou X, Thomas R, Smith AT, Bonner MY, Bakshi P, Banga AK, Bowen JP, Qabaja G, Ford SL, et al: Solenopsin A and analogs exhibit ceramide-like biological activity. Vasc Cell. 7:52015. View Article : Google Scholar : PubMed/NCBI

19 

Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N and Yue Z: Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol. 11:468–476. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Kim JK, Shin EK and Park JH, Kim YH and Park JH: Antitumor and antimetastatic effects of licochalcone A in mouse models. J Mol Med (Berl). 88:829–838. 2010. View Article : Google Scholar

21 

Park JH, Lim HJ, Lee KS, Lee S, Kwak HJ, Cha JH and Park HY: Anti-proliferative effect of licochalcone A on vascular smooth muscle cells. Biol Pharm Bull. 31:1996–2000. 2008. View Article : Google Scholar : PubMed/NCBI

22 

DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, et al: Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature. 475:106–109. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Di Nardo A, Wertz MH, Kwiatkowski E, Tsai PT, Leech JD, Greene-Colozzi E, Goto J, Dilsiz P, Talos DM, Clish CB, et al: Neuronal Tsc1/2 complex controls autophagy through AMPK-dependent regulation of ULK1. Hum Mol Genet. 23:3865–3874. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Chen Y, Nie H, Tian L, Tong L, Deng J, Zhang Y, Dong H and Xiong L: Sevoflurane preconditioning-induced neuroprotection is associated with Akt activation via carboxy-terminal modulator protein inhibition. Br J Anaesth. 114:327–335. 2015. View Article : Google Scholar

25 

Qi Z, Yang W, Liu Y, Cui T, Gao H, Duan C, Lu L, Zhao C, Zhao H and Yang H: Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model. Neurochem Int. 59:572–581. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Niu Q, Zhao W, Wang J, Li C, Yan T, Lv W, Wang G, Duan W, Zhang T, Wang K, Wang K, et al: LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells. Int J Mol Med 41: 2601-2608, 2018.
APA
Niu, Q., Zhao, W., Wang, J., Li, C., Yan, T., Lv, W. ... Zhou, D. (2018). LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells. International Journal of Molecular Medicine, 41, 2601-2608. https://doi.org/10.3892/ijmm.2018.3499
MLA
Niu, Q., Zhao, W., Wang, J., Li, C., Yan, T., Lv, W., Wang, G., Duan, W., Zhang, T., Wang, K., Zhou, D."LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells". International Journal of Molecular Medicine 41.5 (2018): 2601-2608.
Chicago
Niu, Q., Zhao, W., Wang, J., Li, C., Yan, T., Lv, W., Wang, G., Duan, W., Zhang, T., Wang, K., Zhou, D."LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells". International Journal of Molecular Medicine 41, no. 5 (2018): 2601-2608. https://doi.org/10.3892/ijmm.2018.3499
Copy and paste a formatted citation
x
Spandidos Publications style
Niu Q, Zhao W, Wang J, Li C, Yan T, Lv W, Wang G, Duan W, Zhang T, Wang K, Wang K, et al: LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells. Int J Mol Med 41: 2601-2608, 2018.
APA
Niu, Q., Zhao, W., Wang, J., Li, C., Yan, T., Lv, W. ... Zhou, D. (2018). LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells. International Journal of Molecular Medicine, 41, 2601-2608. https://doi.org/10.3892/ijmm.2018.3499
MLA
Niu, Q., Zhao, W., Wang, J., Li, C., Yan, T., Lv, W., Wang, G., Duan, W., Zhang, T., Wang, K., Zhou, D."LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells". International Journal of Molecular Medicine 41.5 (2018): 2601-2608.
Chicago
Niu, Q., Zhao, W., Wang, J., Li, C., Yan, T., Lv, W., Wang, G., Duan, W., Zhang, T., Wang, K., Zhou, D."LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells". International Journal of Molecular Medicine 41, no. 5 (2018): 2601-2608. https://doi.org/10.3892/ijmm.2018.3499
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team