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
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
October 2013 Volume 8 Issue 4

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
October 2013 Volume 8 Issue 4

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

Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway

  • Authors:
    • Yu Zhang
    • Yong Li Bao
    • Yin Wu
    • Chun Lei Yu
    • Yan Xin Huang
    • Ying Sun
    • Li Hua Zheng
    • Yu Xin Li
  • View Affiliations / Copyright

    Affiliations: National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, Jilin 130024, P.R. China, Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education, Normal University, Changchun, Jilin 130024, P.R. China, Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, P.R. China
  • Pages: 967-972
    |
    Published online on: August 16, 2013
       https://doi.org/10.3892/mmr.2013.1640
  • 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

Alantolactone, a methanol extract of Inula helenium, possesses anticancer properties in a number of cancer cell lines. However, its anticancer effect on human colorectal cancer cells and the underlying mechanisms remain to be elucidated. In the present study, the effects of alantolactone on cell viability and apoptosis in RKO human colon cancer cells were investigated. Alantolactone treatment of RKO cells was found to result in dose‑dependent inhibition of cell viability and induction of apoptosis, accompanied with the accumulation of reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential. In addition, these effects were blocked with N‑acetylcysteine, a specific ROS inhibitor. Western blotting indicated that exposure of RKO cells to alantolactone is associated with the downregulation of Bcl‑2, induction of Bax and activation of caspase‑3 and ‑9. These results indicated that a ROS‑mediated mitochondria‑dependent pathway is involved in alantolactone‑induced apoptosis. From these observations, it was hypothesized that alantolactone may be used for the treatment of human colon cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Jemal A, Murray T, Ward E, et al: Cancer statistics, 2005. CA Cancer J Clin. 55:10–30. 2005. View Article : Google Scholar

2 

Gustin DM and Brenner DE: Chemoprevention of colon cancer: current status and future prospects. Cancer Metastasis Rev. 21:323–348. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Fauzi AN, Norazmi MN and Yaacob NS: Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food Chem Toxicol. 49:871–878. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Hsu HF, Houng JY, Kuo CF, Tsao N and Wu YC: Glossogin, a novel phenylpropanoid from Glossogyne tenuifolia, induced apoptosis in A549 lung cancer cells. Food Chem Toxicol. 46:3785–3791. 2008.PubMed/NCBI

5 

Luo M, Liu X, Zu Y, et al: Cajanol, a novel anticancer agent from Pigeonpea [Cajanus cajan (L.) Millsp] roots, induces apoptosis in human breast cancer cells through a ROS-mediated mitochondrial pathway. Chem Biol Interact. 188:151–160. 2010.PubMed/NCBI

6 

Cantrell CL, Abate L, Fronczek FR, et al: Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia subtomentosa. Planta Med. 65:351–355. 1999. View Article : Google Scholar

7 

Konishi T, Shimada Y, Nagao T, Okabe H and Konoshima T: Antiproliferative sesquiterpene lactones from the roots of Inula helenium. Biol Pharm Bull. 25:1370–1372. 2002. View Article : Google Scholar : PubMed/NCBI

8 

Dirsch VM, Stuppner H and Vollmar AM: Cytotoxic sesquiterpene lactones mediate their death-inducing effect in leukemia T cells by triggering apoptosis. Planta Med. 67:557–559. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Lawrence NJ, McGown AT, Nduka J, Hadfield JA and Pritchard RG: Cytotoxic Michael-type amine adducts of alpha-methylene lactones alantolactone and isoalantolactone. Bioorg Med Chem Lett. 11:429–431. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Shi Y, Bao YL, Wu Y, et al: Alantolactone inhibits cell proliferation by interrupting the interaction between Cripto-1 and activin receptor type II A in activin signaling pathway. J Biomol Screen. 16:525–535. 2011. View Article : Google Scholar : PubMed/NCBI

11 

Bellamy CO, Malcomson RD, Harrison DJ and Wyllie AH: Cell death in health and disease: the biology and regulation of apoptosis. Semin Cancer Biol. 6:3–16. 1995. View Article : Google Scholar : PubMed/NCBI

12 

Reed JC: Apoptosis-regulating proteins as targets for drug discovery. Trends Mol Med. 7:314–319. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Kaufmann SH, Kottke TJ, Martins LM, Henzing AJ and Earnshaw WC: Analysis of caspase activation during apoptosis. Curr Protoc Cell Biol. Chapter 18(Unit 18): 22001.PubMed/NCBI

14 

Danial NN and Korsmeyer SJ: Cell death: critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Murphy KM, Ranganathan V, Farnsworth ML, Kavallaris M and Lock RB: Bcl-2 inhibits Bax translocation from cytosol to mitochondria during drug-induced apoptosis of human tumor cells. Cell Death Differ. 7:102–111. 2000. View Article : Google Scholar : PubMed/NCBI

16 

Chatterjee S, Kundu S and Bhattacharyya A: Mechanism of cadmium induced apoptosis in the immunocyte. Toxicol Lett. 177:83–89. 2008. View Article : Google Scholar

17 

Pathak N and Khandelwal S: Role of oxidative stress and apoptosis in cadmium induced thymic atrophy and splenomegaly in mice. Toxicol Lett. 169:95–108. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Martindale JL and Holbrook NJ: Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol. 192:1–15. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Zhou YJ, Zhang SP, Liu CW and Cai YQ: The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells. Toxicol In Vitro. 23:288–294. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Yang JS, Chen GW, Hsia TC, et al: Diallyl disulfide induces apoptosis in human colon cancer cell line (COLO 205) through the induction of reactive oxygen species, endoplasmic reticulum stress, caspases casade and mitochondrial-dependent pathways. Food Chem Toxicol. 47:171–179. 2009. View Article : Google Scholar

21 

Wei A, Zhou D, Xiong C, Cai Y and Ruan J: A novel non-aromatic B-ring flavonoid: isolation, structure elucidation and its induction of apoptosis in human colon HT-29 tumor cell via the reactive oxygen species-mitochondrial dysfunction and MAPK activation. Food Chem Toxicol. 49:2445–2452. 2011. View Article : Google Scholar

22 

Wang L, Xu ML, Hu JH, Rasmussen SK and Wang MH: Codonopsis lanceolata extract induces G0/G1 arrest and apoptosis in human colon tumor HT-29 cells - involvement of ROS generation and polyamine depletion. Food Chem Toxicol. 49:149–154. 2011. View Article : Google Scholar

23 

Zhou L, Bao YL, Zhang Y, et al: Knockdown of TSP50 inhibits cell proliferation and induces apoptosis in P19 cells. IUBMB Life. 62:825–832. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Zhang Y, Zhou L, Bao YL, et al: Butyrate induces cell apoptosis through activation of JNK MAP kinase pathway in human colon cancer RKO cells. Chem Biol Interact. 185:174–181. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Rizzuto R, Nakase H, Darras B, et al: A gene specifying subunit VIII of human cytochrome c oxidase is localized to chromosome 11 and is expressed in both muscle and non-muscle tissues. J Biol Chem. 264:10595–10600. 1989.PubMed/NCBI

26 

Zafarullah M, Li WQ, Sylvester J and Ahmad M: Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci. 60:6–20. 2003. View Article : Google Scholar

27 

Rego AC and Oliveira CR: Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases. Neurochem Res. 28:1563–1574. 2003. View Article : Google Scholar : PubMed/NCBI

28 

Shen Z, Shen J, Chen M, Li Q and Hong C: Morphological changes of mitochondria in apoptosis of esophageal carcinoma cells induced by As(2)O(3). Zhonghua Bing Li Xue Za Zhi. 29:200–203. 2000.(In Chinese).

29 

Gryfe R, Swallow C, Bapat B, et al: Molecular biology of colorectal cancer. Curr Probl Cancer. 21:233–300. 1997. View Article : Google Scholar

30 

Sadowska AM, Manuel Y-Keenoy B and De Backer WA: Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm Pharmacol Ther. 20:9–22. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Budihardjo I, Oliver H, Lutter M, Luo X and Wang X: Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 15:269–290. 1999. View Article : Google Scholar : PubMed/NCBI

32 

Kroemer G and Martin SJ: Caspase-independent cell death. Nat Med. 11:725–730. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Adams JM and Cory S: The Bcl-2 protein family: arbiters of cell survival. Science. 281:1322–1326. 1998. View Article : Google Scholar : PubMed/NCBI

34 

Yin XM: Signal transduction mediated by Bid, a pro-death Bcl-2 family proteins, connects the death receptor and mitochondria apoptosis pathways. Cell Res. 10:161–167. 2000. View Article : Google Scholar : PubMed/NCBI

35 

Nomura M, Shimizu S, Ito T, et al: Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res. 59:5542–5548. 1999.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang Y, Bao YL, Wu Y, Yu CL, Huang YX, Sun Y, Zheng LH and Li YX: Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway. Mol Med Rep 8: 967-972, 2013.
APA
Zhang, Y., Bao, Y.L., Wu, Y., Yu, C.L., Huang, Y.X., Sun, Y. ... Li, Y.X. (2013). Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway. Molecular Medicine Reports, 8, 967-972. https://doi.org/10.3892/mmr.2013.1640
MLA
Zhang, Y., Bao, Y. L., Wu, Y., Yu, C. L., Huang, Y. X., Sun, Y., Zheng, L. H., Li, Y. X."Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway". Molecular Medicine Reports 8.4 (2013): 967-972.
Chicago
Zhang, Y., Bao, Y. L., Wu, Y., Yu, C. L., Huang, Y. X., Sun, Y., Zheng, L. H., Li, Y. X."Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway". Molecular Medicine Reports 8, no. 4 (2013): 967-972. https://doi.org/10.3892/mmr.2013.1640
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang Y, Bao YL, Wu Y, Yu CL, Huang YX, Sun Y, Zheng LH and Li YX: Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway. Mol Med Rep 8: 967-972, 2013.
APA
Zhang, Y., Bao, Y.L., Wu, Y., Yu, C.L., Huang, Y.X., Sun, Y. ... Li, Y.X. (2013). Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway. Molecular Medicine Reports, 8, 967-972. https://doi.org/10.3892/mmr.2013.1640
MLA
Zhang, Y., Bao, Y. L., Wu, Y., Yu, C. L., Huang, Y. X., Sun, Y., Zheng, L. H., Li, Y. X."Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway". Molecular Medicine Reports 8.4 (2013): 967-972.
Chicago
Zhang, Y., Bao, Y. L., Wu, Y., Yu, C. L., Huang, Y. X., Sun, Y., Zheng, L. H., Li, Y. X."Alantolactone induces apoptosis in RKO cells through the generation of reactive oxygen species and the mitochondrial pathway". Molecular Medicine Reports 8, no. 4 (2013): 967-972. https://doi.org/10.3892/mmr.2013.1640
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