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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
July-2017 Volume 14 Issue 1

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
July-2017 Volume 14 Issue 1

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

Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis

  • Authors:
    • Kyung‑Hwa Kang
    • Min Ho Han
    • Jin‑Woo Jeong
    • Cheol Park
    • Sang‑Hyup Lee
    • Hai Woong Lee
    • Sang Hoon Hong
    • Yung Hyun Choi
    • Su Hyun Hong
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Natural Products Research Team, National Marine Biodiversity Institute of Korea, Seocheon, South Chungcheong 325‑902, Republic of Korea, Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Molecular Biology, College of Natural Science and Human Ecology, Dongeui University, Busan 614‑714, Republic of Korea, Department of Korean Medical Classics, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Public Health, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea, Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea
    Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 853-859
    |
    Published online on: May 22, 2017
       https://doi.org/10.3892/ol.2017.6223
  • 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

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, has garnered interest as it is relatively non‑toxic to normal cells, but selectively induces apoptotic cell death in multiple types of transformed or malignant cells. Bufalin is the major digoxin‑like immunoreactive component of Sum Su, which is obtained from the skin and parotid venom gland of the toad. Bufalin is known to inhibit cell proliferation and induce apoptosis in a variety of cancer cells. The present study investigated whether bufalin promoted TRAIL‑induced apoptotic cell death. In the present study, a combined treatment using bufalin and TRAIL significantly increased TRAIL‑mediated inhibition of cell viability and increased apoptosis in T24 human bladder cancer cells. The apoptotic effects were associated with the upregulation of death receptor proteins and the downregulation of cellular Fas‑associated death domain-like interleukin‑1β‑converting enzyme inhibitory protein and X‑linked inhibitor of apoptosis protein. Furthermore, the data revealed that bufalin and TRAIL activated caspase‑3, ‑8 and ‑9 and subsequently increased the degradation of poly (ADP‑ribose) polymerase. Taken altogether, the nontoxic doses of bufalin and TRAIL sensitized T24 cells to TRAIL‑mediated apoptosis. Therefore, bufalin may provide an effective therapeutic strategy for the safe treatment of human bladder cancers that are resistant to TRAIL.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Trivedi R and Mishra DP: Trailing TRAIL resistance: Novel targets for TRAIL sensitization in cancer cells. Front Oncol. 5:692015. View Article : Google Scholar : PubMed/NCBI

2 

Thorburn A, Behbakht K and Ford H: TRAIL receptor-targeted therapeutics: Resistance mechanisms and strategies to avoid them. Drug Resist Updat. 11:17–24. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Dai X, Zhang J, Arfuso F, Chinnathambi A, Zayed ME, Alharbi SA, Kumar AP, Ahn KS and Sethi G: Targeting TNF-related apoptosis-inducing ligand (TRAIL) receptor by natural products as a potential therapeutic approach for cancer therapy. Exp Biol Med (Maywood). 240:760–773. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Szliszka E, Mazur B, Zydowicz G, Czuba ZP and Król W: TRAIL-induced apoptosis and expression of death receptor TRAIL-R1 and TRAIL-R2 in bladder cancer cells. Folia Histochem Cytobiol. 47:579–585. 2009.PubMed/NCBI

5 

Lim B, Allen JE, Prabhu VV, Talekar MK, Finnberg NK and El-Deiry WS: Targeting TRAIL in the treatment of cancer: New developments. Expert Opin Ther Targets. 19:1171–1185. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Chen S, Fu L, Raja SM, Yue P, Khuri FR and Sun SY: Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of Geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis. Mol Cancer. 9:232010. View Article : Google Scholar : PubMed/NCBI

7 

Wang S and El-Deiry WS: TRAIL and apoptosis induction by TNF-family death receptors. Oncogene. 22:8628–8633. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Guancial EA, Roussel B, Bergsma DP, Bylund KC, Sahasrabudhe D, Messing E, Mohile SG and Fung C: Bladder cancer in the elderly patient: Challenges and solutions. Clin Interv Aging. 10:939–949. 2015.PubMed/NCBI

9 

Shamseddine A, Saleh A, Charafeddine M, Seoud M, Mukherji D, Temraz S and Sibai AM: Cancer trends in Lebanon: A review of incidence rates for the period of 2003–2008 and projections until 2018. Popul Health Metr. 12:42014. View Article : Google Scholar : PubMed/NCBI

10 

Ahmed SM, Wu X, Jin X, Zhang X, Togo Y, Suzuki T, Li Y, Kanematsu A, Nojima M, Yamamoto S, et al: Synergistic induction of apoptosis by mapatumumab and anthracyclines in human bladder cancer cells. Oncol Rep. 33:566–572. 2015.PubMed/NCBI

11 

Ploeg M, Aben KK and Kiemeney LA: The present and future burden of urinary bladder cancer in the world. World J Urol. 27:289–293. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Yan S, Qu X, Xu L, Che X, Ma Y, Zhang L, Teng Y, Zou H and Liu Y: Bufalin enhances TRAIL-induced apoptosis by redistributing death receptors in lipid rafts in breast cancer cells. Anticancer Drugs. 25:683–689. 2014.PubMed/NCBI

13 

White-Gilbertson SJ, Kasman L, McKillop J, Tirodkar T, Lu P and Voelkel-Johnson C: Oxidative stress sensitizes bladder cancer cells to TRAIL mediated apoptosis by down-regulating anti-apoptotic proteins. J Urol. 182:1178–1185. 2009. View Article : Google Scholar : PubMed/NCBI

14 

LeBlanc H, Lawrence D, Varfolomeev E, Totpal K, Morlan J, Schow P, Fong S, Schwall R, Sinicropi D and Ashkenazi A: Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med. 8:274–281. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Shi YL, Feng S, Chen W, Hua ZC, Bian JJ and Yin W: Mitochondrial inhibitor sensitizes non-small-cell lung carcinoma cells to TRAIL-induced apoptosis by reactive oxygen species and Bcl-X(L)/p53-mediated amplification mechanisms. Cell Death Dis. 5:e15792014. View Article : Google Scholar : PubMed/NCBI

16 

Yin PH, Liu X, Qiu YY, Cai JF, Qin JM, Zhu HR and Li Q: Anti-tumor activity and apoptosis-regulation mechanisms of bufalin in various cancers: New hope for cancer patients. Asian Pac J Cancer Prev. 13:5339–5343. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Qi F, Li A, Inagaki Y, Kokudo N, Tamura S, Nakata M and Tang W: Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol. 11:342–349. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Huang WW, Yang JS, Pai SJ, Wu PP, Chang SJ, Chueh FS, Fan MJ, Chiou SM, Kuo HM, Yeh CC, et al: Bufalin induces G0/G1 phase arrest through inhibiting the levels of cyclin Dcyclin E, CDK2 and CDK4, and triggers apoptosis via mitochondrial signaling pathway in T24 human bladder cancer cells. Mutat Res. 732:26–33. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Takai N, Ueda T, Nishida M, Nasu K and Narahara H: Bufalin induces growth inhibition, cell cycle arrest and apoptosis in human endometrial and ovarian cancer cells. Int J Mol Med. 21:637–643. 2008.PubMed/NCBI

20 

Yeh JY, Huang WJ, Kan SF and Wang PS: Effects of bufalin and cinobufagin on the proliferation of androgen dependent and independent prostate cancer cells. Prostate. 54:112–124. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Yan S, Qu X, Xu C, Zhu Z, Zhang L, Xu L, Song N, Teng Y and Liu Y: Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 138:1279–1289. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Kelley RF, Totpal K, Lindstrom SH, Mathieu M, Billeci K, Deforge L, Pai R, Hymowitz SG and Ashkenazi A: Receptor-selective mutants of apoptosis-inducing ligand 2/tumor necrosis factor- related apoptosis-inducing ligand reveal a greater contribution of death receptor (DR) 5 than DR4 to apoptosis signaling. J Biol Chem. 280:2205–2212. 2005. View Article : Google Scholar : PubMed/NCBI

23 

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

24 

Shalini S, Dorstyn L, Dawar S and Kumar S: Old, new and emerging functions of caspases. Cell Death Differ. 22:526–539. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Jin CY, Park C, Hwang HJ, Kim GY, Choi BT, Kim WJ and Choi YH: Naringenin up-regulates the expression of death receptor 5 and enhances TRAIL-induced apoptosis in human lung cancer A549 cells. Mol Nutr Food Res. 55:300–309. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Hong SH and Choi YH: Bufalin induces apoptosis through activation of both the intrinsic and extrinsic pathways in human bladder cancer cells. Oncol Rep. 27:114–120. 2012.PubMed/NCBI

27 

Li Y, Jin X, Li J, Jin X, Yu J, Sun X, Chu Y, Xu C, Li X, Wang X, et al: Expression of TRAIL, DR4, and DR5 in bladder cancer: Correlation with response to adjuvant therapy and implications of prognosis. Urology. 79:968.e7–e15. 2012. View Article : Google Scholar

28 

Wu GS: TRAIL as a target in anti-cancer therapy. Cancer Lett. 285:1–5. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Chen Z, Sangwan V, Banerjee S, Chugh R, Dudeja V, Vickers SM and Saluja AK: Triptolide sensitizes pancreatic cancer cells to TRAIL-induced activation of the death receptor pathway. Cancer Lett. 348:156–166. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Safa AR: c-FLIP, a master anti-apoptotic regulator. Exp Oncol. 34:176–184. 2012.PubMed/NCBI

31 

Ewald F, Ueffing N, Brockmann L, Hader C, Telieps T, Schuster M, Schulz WA and Schmitz I: The role of c-FLIP splice variants in urothelial tumours. Cell Death Dis. 2:e2452011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Kang KH, Han MH, Jeong JW, Park C, Lee SH, Lee HW, Hong SH, Choi YH and Hong SH: Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis. Oncol Lett 14: 853-859, 2017.
APA
Kang, K., Han, M.H., Jeong, J., Park, C., Lee, S., Lee, H.W. ... Hong, S.H. (2017). Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis. Oncology Letters, 14, 853-859. https://doi.org/10.3892/ol.2017.6223
MLA
Kang, K., Han, M. H., Jeong, J., Park, C., Lee, S., Lee, H. W., Hong, S. H., Choi, Y. H., Hong, S. H."Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis". Oncology Letters 14.1 (2017): 853-859.
Chicago
Kang, K., Han, M. H., Jeong, J., Park, C., Lee, S., Lee, H. W., Hong, S. H., Choi, Y. H., Hong, S. H."Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis". Oncology Letters 14, no. 1 (2017): 853-859. https://doi.org/10.3892/ol.2017.6223
Copy and paste a formatted citation
x
Spandidos Publications style
Kang KH, Han MH, Jeong JW, Park C, Lee SH, Lee HW, Hong SH, Choi YH and Hong SH: Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis. Oncol Lett 14: 853-859, 2017.
APA
Kang, K., Han, M.H., Jeong, J., Park, C., Lee, S., Lee, H.W. ... Hong, S.H. (2017). Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis. Oncology Letters, 14, 853-859. https://doi.org/10.3892/ol.2017.6223
MLA
Kang, K., Han, M. H., Jeong, J., Park, C., Lee, S., Lee, H. W., Hong, S. H., Choi, Y. H., Hong, S. H."Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis". Oncology Letters 14.1 (2017): 853-859.
Chicago
Kang, K., Han, M. H., Jeong, J., Park, C., Lee, S., Lee, H. W., Hong, S. H., Choi, Y. H., Hong, S. H."Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis". Oncology Letters 14, no. 1 (2017): 853-859. https://doi.org/10.3892/ol.2017.6223
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