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
January-2020 Volume 19 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
January-2020 Volume 19 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

β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway

  • Authors:
    • Daoju Gan
    • Weiyang He
    • Hubin Yin
    • Xin Gou
  • View Affiliations / Copyright

    Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China
    Copyright: © Gan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 291-300
    |
    Published online on: November 14, 2019
       https://doi.org/10.3892/ol.2019.11103
  • 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

Cisplatin‑based chemotherapy is the standard regimen for patients with bladder cancer, but its effectiveness is limited by high toxicity and the development of drug resistance. β‑elemene (β‑ELE), a compound extracted from Rhizoma zedoariae, has antitumor activity in various malignancies and exhibits low toxicity. However, the effects and specific mechanism of β‑ELE in bladder cancer remain unclear. The present study aimed to investigate the antitumor activity and possible mechanisms of β‑ELE alone and in combination with cisplatin in bladder cancer cells. Cell viability was determined using Cell Counting Kit‑8. Cell cycle and reactive oxygen species (ROS) analyses were performed by flow cytometry. Apoptosis was detected by Hoechst 33258 and Annexin‑V/propidium iodide staining. Mitochondrial membrane potential was determined by staining with a JC‑1 probe, flow cytometry and fluorescence microscopy. Protein expression was detected by western blotting. The results revealed that β‑ELE significantly inhibited the proliferation of various bladder cancer cell lines and induced cell cycle arrest at G0/G1‑phase in T24 and 5637 cells. Compared with cisplatin alone, co‑treatment with β‑ELE increased cisplatin‑mediated cytotoxicity against T24 cells, which resulted in the loss of mitochondrial membrane potential and release of cytochrome c into the cytoplasm. Co‑treatment with β‑ELE and cisplatin enhanced ROS accumulation and activation of 5'AMP‑activated protein kinase (AMPK), which induced apoptosis. The results of the present study suggested that β‑ELE inhibited the proliferation of bladder cancer cells in vitro and enhanced cisplatin‑induced mitochondria‑dependent apoptosis via the ROS‑AMPK signaling pathway. Combination therapy with β‑ELE requires further investigation as a potential treatment of bladder cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI

2 

Yin H, He W, Li Y, Xu N, Zhu X, Lin Y and Gou X: Loss of DUSP2 predicts a poor prognosis in patients with bladder cancer. Hum Pathol. 85:152–161. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Lamm D, Persad R, Brausi M, Buckley R, Witjes JA, Palou J, Böhle A, Kamat AM, Colombel M and Soloway M: Defining progression in nonmuscle invasive bladder cancer: It is time for a new, standard definition. J Urol. 191:20–27. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Dasari S and Tchounwou PB: Cisplatin in cancer therapy: Molecular mechanisms of action. Eur J Pharmacol. 740:364–378. 2014. View Article : Google Scholar : PubMed/NCBI

5 

Tan W, Lu J, Huang M, Li Y, Chen M, Wu G, Gong J, Zhong Z, Xu Z, Dang Y, et al: Anti-cancer natural products isolated from chinese medicinal herbs. Chin Med. 6:272011. View Article : Google Scholar : PubMed/NCBI

6 

Zhai B, Zeng Y, Zeng Z, Zhang N, Li C, Zeng Y, You Y, Wang S, Chen X, Sui X and Xie T: Drug delivery systems for elemene, its main active ingredient β-elemene, and its derivatives in cancer therapy. Int J Nanomedicine. 13:6279–6296. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Liu J, Zhang Y, Qu J, Xu L, Hou K, Zhang J, Qu X and Liu Y: β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis. BMC Cancer. 11:1832011. View Article : Google Scholar : PubMed/NCBI

8 

Jiang Z, Jacob JA, Loganathachetti DS, Nainangu P and Chen B: β-elemene: Mechanistic studies on cancer cell interaction and its chemosensitization effect. Front Pharmacol. 8:1052017. View Article : Google Scholar : PubMed/NCBI

9 

Lu X, Wang Y, Luo H, Qiu W, Han H, Chen X and Yang L: β-elemene inhibits the proliferation of T24 bladder carcinoma cells through upregulation of the expression of Smad4. Mol Med Rep. 7:513–518. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Li QQ, Wang G, Liang H, Li JM, Huang F, Agarwal PK, Zhong Y and Reed E: β-elemene promotes cisplatin-induced cell death in human bladder cancer and other carcinomas. Anticancer Res. 33:1421–1428. 2013.PubMed/NCBI

11 

Koosha S, Mohamed Z, Sinniah A, Ibrahim ZA, Seyedan A and Alshawsh MA: Antiproliferative and apoptotic activities of 8-prenylnaringenin against human colon cancer cells. Life Sci. 232:1166332019. View Article : Google Scholar : PubMed/NCBI

12 

Goldar S, Khaniani MS, Derakhshan SM and Baradaran B: Molecular mechanisms of apoptosis and roles in cancer development and treatment. Asian Pac J Cancer Prev. 16:2129–2144. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Li X, Lin Z, Zhang B, Guo L, Liu S, Li H, Zhang J and Ye Q: β-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1. Sci Rep. 6:210102016. View Article : Google Scholar : PubMed/NCBI

14 

Cai B, Ma L, Nong S, Wu Y, Guo X and Pu J: β-elemene induced anticancer effect in bladder cancer through upregulation of PTEN and suppression of AKT phosphorylation. Oncol Lett. 16:6019–6025. 2018.PubMed/NCBI

15 

Li QQ, Lee RX, Liang H, Zhong Y and Reed E: Enhancement of cisplatin-induced apoptosis by β-elemene in resistant human ovarian cancer cells. Med Oncol. 30:4242013. View Article : Google Scholar : PubMed/NCBI

16 

Park BH, Lim JE, Jeon HG, Seo SI, Lee HM, Choi HY, Jeon SS and Jeong BC: Curcumin potentiates antitumor activity of cisplatin in bladder cancer cell lines via ROS-mediated activation of ERK1/2. Oncotarget. 7:63870–63886. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Ren Y and Shen HM: Critical role of AMPK in redox regulation under glucose starvation. Redox Biol. 1011542019.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI

18 

von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A and Arning M: Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol. 23:4602–4608. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Liu Y, Jiang ZY, Zhou YL, Qiu HH, Wang G, Luo Y, Liu JB, Liu XW, Bu WQ, Song J, et al: β-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway. Biomed Pharmacother. 93:490–497. 2017. View Article : Google Scholar : PubMed/NCBI

20 

Mao Y, Zhang J, Hou L and Cui X: The effect of beta-elemene on alpha-tubulin polymerization in human hepatoma HepG2 cells. Chin J Cancer Res. 25:770–776. 2013.PubMed/NCBI

21 

Lee RX, Li QQ and Reed E: β-elemene effectively suppresses the growth and survival of both platinum-sensitive and -resistant ovarian tumor cells. Anticancer Res. 32:3103–3113. 2012.PubMed/NCBI

22 

Wu J, Tang Q, Yang L, Chen Y, Zheng F and Hann SS: Interplay of DNA methyltransferase 1 and EZH2 through inactivation of Stat3 contributes to β-elemene-inhibited growth of nasopharyngeal carcinoma cells. Sci Rep. 7:5092017. View Article : Google Scholar : PubMed/NCBI

23 

Yao S, Xu J, Zhao K, Song P, Yan Q, Fan W, Li W and Lu C: Down-regulation of HPGD by miR-146b-3p promotes cervical cancer cell proliferation, migration and anchorage-independent growth through activation of STAT3 and AKT pathways. Cell Death Dis. 9:10552018. View Article : Google Scholar : PubMed/NCBI

24 

Liu S, Zhou L, Zhao Y and Yuan Y: β-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway. Oncol Rep. 34:943–951. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Huang C and Yu Y: Synergistic cytotoxicity of β-elemene and cisplatin in gingival squamous cell carcinoma by inhibition of STAT3 signaling pathway. Med Sci Monit. 23:1507–1513. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Zhang J, Zhang HD, Yao YF, Zhong SL, Zhao JH and Tang JH: β-elemene reverses chemoresistance of breast cancer cells by reducing resistance transmission via exosomes. Cell Physiol Biochem. 36:2274–2286. 2015. View Article : Google Scholar : PubMed/NCBI

27 

Kruk J, Aboul-Enein HY, Kładna A and Bowser JE: Oxidative stress in biological systems and its relation with pathophysiological functions: The effect of physical activity on cellular redox homeostasis. Free Radic Res. 53:497–521. 2019. View Article : Google Scholar : PubMed/NCBI

28 

Li X, Wang H, Wang J, Chen Y, Yin X, Shi G, Li H, Hu Z and Liang X: Emodin enhances cisplatin-induced cytotoxicity in human bladder cancer cells through ROS elevation and MRP1 downregulation. BMC Cancer. 16:5782016. View Article : Google Scholar : PubMed/NCBI

29 

Shaw RJ, Kosmatka M, Bardeesy N, Hurley RL, Witters LA, DePinho RA and Cantley LC: The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress. Proc Natl Acad Sci USA. 101:3329–3335. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Woods A, Dickerson K, Heath R, Hong SP, Momcilovic M, Johnstone SR, Carlson M and Carling D: Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab. 2:21–33. 2005. View Article : Google Scholar : PubMed/NCBI

31 

Emerling BM, Weinberg F, Snyder C, Burgess Z, Mutlu GM, Viollet B, Budinger GR and Chandel NS: Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radic Biol Med. 46:1386–1391. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Zhao S, Wu J, Zheng F, Tang Q, Yang L, Li L, Wu W and Hann SS: β-elemene inhibited expression of DNA methyltransferase 1 through activation of ERK1/2 and AMPKα signalling pathways in human lung cancer cells: The role of Sp1. J Cell Mol Med. 19:630–641. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Han M, Gao H, Xie J, Yuan YP, Yuan Q, Gao MQ, Liu KL, Chen XH, Han YT and Han ZW: Hispidulin induces ER stress-mediated apoptosis in human hepatocellular carcinoma cells in vitro and in vivo by activating AMPK signaling pathway. Acta Pharmacol Sin. 40:666–676. 2019. View Article : Google Scholar : PubMed/NCBI

34 

Lu CC, Chiang JH, Tsai FJ, Hsu YM, Juan YN, Yang JS and Chiu HY: Metformin triggers the intrinsic apoptotic response in human AGS gastric adenocarcinoma cells by activating AMPK and suppressing mTOR/AKT signaling. Int J Oncol. 54:1271–1281. 2019.PubMed/NCBI

35 

Zhai B, Zhang N, Han X, Li Q, Zhang M, Chen X, Li G, Zhang R, Chen P, Wang W, et al: Molecular targets of β-elemene, a herbal extract used in traditional Chinese medicine, and its potential role in cancer therapy: A review. Biomed Pharmacother. 114:1088122019. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Gan D, He W, Yin H and Gou X: β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway. Oncol Lett 19: 291-300, 2020.
APA
Gan, D., He, W., Yin, H., & Gou, X. (2020). β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway. Oncology Letters, 19, 291-300. https://doi.org/10.3892/ol.2019.11103
MLA
Gan, D., He, W., Yin, H., Gou, X."β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway". Oncology Letters 19.1 (2020): 291-300.
Chicago
Gan, D., He, W., Yin, H., Gou, X."β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway". Oncology Letters 19, no. 1 (2020): 291-300. https://doi.org/10.3892/ol.2019.11103
Copy and paste a formatted citation
x
Spandidos Publications style
Gan D, He W, Yin H and Gou X: β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway. Oncol Lett 19: 291-300, 2020.
APA
Gan, D., He, W., Yin, H., & Gou, X. (2020). β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway. Oncology Letters, 19, 291-300. https://doi.org/10.3892/ol.2019.11103
MLA
Gan, D., He, W., Yin, H., Gou, X."β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway". Oncology Letters 19.1 (2020): 291-300.
Chicago
Gan, D., He, W., Yin, H., Gou, X."β‑elemene enhances cisplatin‑induced apoptosis in bladder cancer cells through the ROS‑AMPK signaling pathway". Oncology Letters 19, no. 1 (2020): 291-300. https://doi.org/10.3892/ol.2019.11103
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