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
June-2015 Volume 35 Issue 6

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
June-2015 Volume 35 Issue 6

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

Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway

  • Authors:
    • Xudong Xu
    • Da Chen
    • Bo Ye
    • Fangming Zhong
    • Gang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic Surgery, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang 310000, P.R. China
  • Pages: 1610-1616
    |
    Published online on: April 2, 2015
       https://doi.org/10.3892/ijmm.2015.2167
  • 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

Curcumin is known for its anti-proliferative effects in lung cancer cells. Studies have demonstrated that an increase in the levels of intracellular free calcium ([Ca2+]i) is involved in curcumin-induced apoptosis. In this study, we aimed to investigate the involvement of calcium overload in the anti-proliferative effects of curcumin on lung cancer cells and the possible mechanisms involved. A549 and H1299 lung cancer cells were incubated with serial diluted curcumin. MTT assay was used to assess the cytotoxic effects of curcumin on the lung cancer cells; the inositol 1,4,5-trisphosphate receptor (IP3R, a key regulator of [Ca2+]i signaling) was blocked by its specific inhibitor, xestospongin C (XSC). Hoechst 33342, Fura-2/AM and rhodamine 123 fluorescence staining was employed to detect the apoptosis, the [Ca2+]i level and mitochondrial potential in the lung cancer cells. The expression levels of B-cell lymphoma-2 (Bcl‑2), cleaved caspase-3 and cleaved caspase-9, and the phosphorylation level of IP3R were evaluated by western blot analysis. Our results revealed that curcumin inhibited cell growth, increased the [Ca2+]i level and increased the apoptosis of the lung cancer cells in a concentration-dependent manner. However, XSC attenuated the increase in the [Ca2+]i level and apoptosis, and also reversed the curcumin-induced loss of mitochondrial potential potential. Treatment with curcumin downregulated the expression of Bcl-2, and elevated the phosphorylation level of IP3R in a concentration-dependent manner. However, this effect was not reversed by treatment with XSC. In conclusion, the cytotoxic effects of curcumin on lung cancer cells were induced by calcium overload, which involves Bcl-2 mediated IP3R phosphorylation.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Ike S, Tanaka F, Ueda M, et al: Evaluation of improvement in prognosis in surgical cases of lung cancer based on the 5-year survival rate. Nippon Kyobu Geka Gakkai Zasshi. 44:312–313. 1996.In Japanese.

2 

Hung JJ, Jeng WJ, Hsu WH, Chou TY, Huang BS and Wu YC: Predictors of death, local recurrence, and distant metastasis in completely resected pathological stage-I non-small-cell lung cancer. J Thorac Oncol. 7:1115–1123. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Saisho S, Yasuda K, Maeda A, et al: Post-recurrence survival of patients with non-small-cell lung cancer after curative resection with or without induction/adjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 16:166–172. 2013. View Article : Google Scholar :

4 

Li JH, Yue W, Huang Z, et al: Calcium overload induces C6 rat glioma cell apoptosis in sonodynamic therapy. Int J Radiat Biol. 87:1061–1066. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Nakayama H, Fujio Y and Yamaguchi O: Calcium dependent signaling in cardiac hypertrophy and cell death. Clin Calcium. 23:505–515. 2013.In Japanese. PubMed/NCBI

6 

Seo SR and Seo JT: Calcium overload is essential for the acceleration of staurosporine-induced cell death following neuronal differentiation in PC12 cells. Exp Mol Med. 41:269–276. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Ma TS: Sarcoplasmic reticulum calcium ATPase overexpression induces cellular calcium overload and cell death. Ann NY Acad Sci. 853:325–328. 1998. View Article : Google Scholar

8 

Johnson GG, White MC and Grimaldi M: Stressed to death: targeting endoplasmic reticulum stress response induced apoptosis in gliomas. Curr Pharm Des. 17:284–292. 2011. View Article : Google Scholar : PubMed/NCBI

9 

He Q, Lee DI, Rong R, et al: Endoplasmic reticulum calcium pool depletion-induced apoptosis is coupled with activation of the death receptor 5 pathway. Oncogene. 21:2623–2633. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Deniaud A, Sharaf el dein O, Maillier E, et al: Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis. Oncogene. 27:285–299. 2008. View Article : Google Scholar

11 

Kasumu AW, Liang X, Egorova P, Vorontsova D and Bezprozvanny I: Chronic suppression of inositol 1,4,5-triphosphate receptor-mediated calcium signaling in cerebellar purkinje cells alleviates pathological phenotype in spinocerebellar ataxia 2 mice. J Neurosci. 32:12786–12796. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Rong YP, Aromolaran AS, Bultynck G, et al: Targeting Bcl-2-IP3 receptor interaction to reverse Bcl-2’s inhibition of apoptotic calcium signals. Mol Cell. 31:255–265. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Puliyappadamba VT, Cheriyan VT, Thulasidasan AK, et al: Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent. Mol Cancer. 9:2202010. View Article : Google Scholar : PubMed/NCBI

14 

Wang WH, Chiang IT, Ding K, et al: Curcumin-induced apoptosis in human hepatocellular carcinoma j5 cells: Critical role of ca(+2)-dependent pathway. Evid Based Complement Alternat Med. 2012:5129072012. View Article : Google Scholar : PubMed/NCBI

15 

Zi X and Zhang R: Anti-cancer molecular targets of natural products. Curr Cancer Drug Targets. 13:4852013. View Article : Google Scholar : PubMed/NCBI

16 

Cragg GM, Grothaus PG and Newman DJ: Impact of natural products on developing new anti-cancer agents. Chem Rev. 109:3012–3043. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Sun W, Wang W, Kim J, et al: Anti-cancer effect of resveratrol is associated with induction of apoptosis via a mitochondrial pathway alignment. Adv Exp Med Biol. 614:179–186. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Wang W, Rayburn ER, Hao M, et al: Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides. Prostate. 68:809–819. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Liu XY, Ruan LM, Mao WW, Wang JQ, Shen YQ and Sui MH: Preparation of RGD-modified long circulating liposome loading matrine, and its in vitro anti-cancer effects. Int J Med Sci. 7:197–208. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Franek KJ, Zhou Z, Zhang WD and Chen WY: In vitro studies of baicalin alone or in combination with Salvia miltiorrhiza extract as a potential anticancer agent. Int J Oncol. 26:217–224. 2005.

21 

Noorafshan A and Ashkani-Esfahani S: A review of therapeutic effects of curcumin. Curr Pharm Des. 19:2032–2046. 2013.

22 

Mehta HJ, Patel V and Sadikot RT: Curcumin and lung cancer-a review. Target Oncol. May 21–2014.Epub ahead of print. View Article : Google Scholar

23 

Darvesh AS, Aggarwal BB and Bishayee A: Curcumin and liver cancer: a review. Curr Pharm Biotechnol. 13:218–228. 2012. View Article : Google Scholar

24 

Jiang L, Liu Y, Ma MM, Tang YB, Zhou JG and Guan YY: Mitochondria dependent pathway is involved in the protective effect of bestrophin-3 on hydrogen peroxide-induced apoptosis in basilar artery smooth muscle cells. Apoptosis. 18:556–565. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Sawai H and Domae N: Release of cytochrome c from mitochondria precedes Bax translocation/activation in Triton X-100-induced apoptosis. Leuk Res. 32:445–453. 2008. View Article : Google Scholar

26 

Wang S and El-Deiry WS: Cytochrome c: a crosslink between the mitochondria and the endoplasmic reticulum in calcium-dependent apoptosis. Cancer Biol Ther. 3:44–46. 2004. View Article : Google Scholar : PubMed/NCBI

27 

Zamzami N and Kroemer G: Methods to measure membrane potential and permeability transition in the mitochondria during apoptosis. Methods Mol Biol. 282:103–115. 2004.PubMed/NCBI

28 

Soengas MS, Alarcon RM, Yoshida H, et al: Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science. 284:156–159. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Pinton P, Giorgi C, Siviero R, Zecchini E and Rizzuto R: Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene. 27:6407–6418. 2008. View Article : Google Scholar : PubMed/NCBI

30 

Kurskii MD, Tugai VA and Fedoriv AN: Effect of serotonin and calcium on separate components of respiratory chain of mitochondria in some rabbit tissues. Ukr Biokhim Zh. 42:584–588. 1970.In Ukrainian.

31 

Komary Z, Tretter L and Adam-Vizi V: Membrane potential-related effect of calcium on reactive oxygen species generation in isolated brain mitochondria. Biochim Biophys Acta. 1797:922–928. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Vanderheyden V, Devogelaere B, Missiaen L, De Smedt H, Bultynck G and Parys JB: Regulation of inositol 1,4,5-trispho-sphate-induced Ca2+ release by reversible phosphorylation and dephosphorylation. Biochim Biophys Acta. 1793:959–970. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Giorgi C, Wieckowski MR, Pandolfi PP and Pinton P: Mitochondria associated membranes (MAMs) as critical hubs for apoptosis. Commun Integr Biol. 4:334–335. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Hahn P, Lindsten T, Ying GS, et al: Proapoptotic bcl-2 family members, Bax and Bak, are essential for developmental photo-receptor apoptosis. Invest Ophthalmol Vis Sci. 44:3598–3605. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Rong YP, Bultynck G, Aromolaran AS, et al: The BH4 domain of Bcl-2 inhibits ER calcium release and apoptosis by binding the regulatory and coupling domain of the IP3 receptor. Proc Natl Acad Sci USA. 106:14397–14402. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Hanson CJ, Bootman MD, Distelhorst CW, Wojcikiewicz RJ and Roderick HL: Bcl-2 suppresses Ca2+ release through inositol 1,4,5-trisphosphate receptors and inhibits Ca2+ uptake by mitochondria without affecting ER calcium store content. Cell Calcium. 44:324–338. 2008. View Article : Google Scholar : PubMed/NCBI

37 

Chen R, Valencia I, Zhong F, et al: Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol. 166:193–203. 2004. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Xu X, Chen D, Ye B, Zhong F and Chen G: Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway. Int J Mol Med 35: 1610-1616, 2015.
APA
Xu, X., Chen, D., Ye, B., Zhong, F., & Chen, G. (2015). Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway. International Journal of Molecular Medicine, 35, 1610-1616. https://doi.org/10.3892/ijmm.2015.2167
MLA
Xu, X., Chen, D., Ye, B., Zhong, F., Chen, G."Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway". International Journal of Molecular Medicine 35.6 (2015): 1610-1616.
Chicago
Xu, X., Chen, D., Ye, B., Zhong, F., Chen, G."Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway". International Journal of Molecular Medicine 35, no. 6 (2015): 1610-1616. https://doi.org/10.3892/ijmm.2015.2167
Copy and paste a formatted citation
x
Spandidos Publications style
Xu X, Chen D, Ye B, Zhong F and Chen G: Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway. Int J Mol Med 35: 1610-1616, 2015.
APA
Xu, X., Chen, D., Ye, B., Zhong, F., & Chen, G. (2015). Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway. International Journal of Molecular Medicine, 35, 1610-1616. https://doi.org/10.3892/ijmm.2015.2167
MLA
Xu, X., Chen, D., Ye, B., Zhong, F., Chen, G."Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway". International Journal of Molecular Medicine 35.6 (2015): 1610-1616.
Chicago
Xu, X., Chen, D., Ye, B., Zhong, F., Chen, G."Curcumin induces the apoptosis of non-small cell lung cancer cells through a calcium signaling pathway". International Journal of Molecular Medicine 35, no. 6 (2015): 1610-1616. https://doi.org/10.3892/ijmm.2015.2167
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