Skip to main content
SpringerLink
Log in

Effects of Agarum clathratum extract on cell death and calcium ion levels of ovarian cancer cell

  • Original Article
  • Published:
Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

In recent years, marine algae are receiving attention due to their health benefits such as anti-oxidative, anti-bacterial, anti-inflammatory, and anti-cancer effects. Agarum clathratum is also known as sieve kelp. As a type of brown algae, it grows on rocks across northwest Pacific to the northwest Atlantic Ocean. A few studies have reported that Agarum clathratum possesses anti-inflammatory and neuroprotective properties. However, unlike other marine algae such as Laminaria japonica or Undaria pinnatifida, therapeutic effects of Agarum clathratum have not been extensively studied yet.

Objectives

Therefore, the objective of the present study was to investigate inhibitory effects of Agarum clathratum on viability of epithelial ovarian cancer ES2 and OV90 cells in vitro.

Results

Agarum clathratum extract (ACE) suppressed the viability of ES2 and OV90 epithelial ovarian cancer cells. In addition, ACE disrupted the mitochondrial membrane potential (MMP) in both ES2 and OV90 cells. Moreover, in ACE-treated ES2 cells, intracellular and mitochondrial Ca2+ were accumulated. In contrast, the level of Ca2+ in the cytosol was slightly decreased. Mitochondrial Ca2+ levels showed no significant changes after ACE treatment. Regarding changes in PI3K/AKT and MAPK signaling pathways, results showed reduction in phosphorylation of AKT and S6 proteins after ACE treatment, indicating that ACE could inhibit the PI3K/AKT pathway. Western blot analysis revealed that the phosphorylation of ERK1/2 MAPK proteins was also decreased after ACE treatment. In contrast, the phosphorylation of JNK and the cytochrome c release were increased by ACE treatment.

Conclusion

Taken together, our findings suggest that ACE might possess anti-cancer effects on epithelial ovarian cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Anderson P (1997) Kinase cascades regulating entry into apoptosis. Microbiol Mol Biol Rev 61:33–46

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boo GH, Lindstrom SC, Klochkova NG, Yotsukura N, Yang EC, Kim HG, Waaland JR, Cho GY, Miller KA, Boo SM (2011) Taxonomy and biogeography of Agarum and Thalassiophyllum (Laminariales, Phaeophyceae) based on sequences of nuclear, mitochondrial, and plastid markers. Taxon 60:831–840

    Article  Google Scholar 

  • Chang F, Lee JT, Navolanic PM, Steelman LS, Shelton JG, Blalock WL, Franklin RA, McCubrey JA (2003) Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia 17:590–603

    Article  CAS  PubMed  Google Scholar 

  • Choo GS, Lee HN, Shin SA, Kim HJ, Jung JY (2016) Anticancer Effect of Fucoidan on DU-145 Prostate Cancer Cells through Inhibition of PI3K/Akt and MAPK Pathway Expression. Mar Drugs 14

  • Doubeni CA, Doubeni AR, Myers AE (2016) Diagnosis and management of ovarian cancer. Am Fam Phys 93:937–944

    Google Scholar 

  • Ersahin T, Tuncbag N, Cetin-Atalay R (2015) The PI3K/AKT/mTOR interactive pathway. Mol Biosyst 11:1946–1954

    Article  CAS  PubMed  Google Scholar 

  • Gao LL, Li FR, Jiao P, Yao ST, Sang H, Si YH (2011) Apoptosis of human ovarian cancer cells induced by Paris chinensis dioscin via a Ca(2+)-mediated mitochondrion pathway. Asian Pac J Cancer Prev 12:1361–1366

    PubMed  Google Scholar 

  • Giorgi C, Baldassari F, Bononi A, Bonora M, De Marchi E, Marchi S, Missiroli S, Patergnani S, Rimessi A, Suski JM, Wieckowski MR, Pinton P (2012) Mitochondrial Ca(2+) and apoptosis. Cell Calcium 52:36–43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han J-M, Cho S-D, Chung G-H, Choi S-J, Shin J, Hong S-D, Hong K-O (2021) Agarum clathratum Inhibits LPS-induced IL-1β Expression through the Regulation of the JNK/c-Jun Signaling Pathway. Korean J Oral Maxillofacial Pathol 45:111–120

    Article  Google Scholar 

  • Jafari M, Ghadami E, Dadkhah T, Akhavan-Niaki H (2019) PI3k/AKT signaling pathway: erythropoiesis and beyond. J Cell Physiol 234:2373–2385

    Article  CAS  PubMed  Google Scholar 

  • Kim IH, Yoo KY, Park JH, Yan BC, Ahn JH, Lee JC, Kwon HM, Kim JD, Kim YM, You SG, Kang IJ, Won MH (2014) Comparison of neuroprotective effects of extract and fractions from Agarum clathratum against experimentally induced transient cerebral ischemic damage. Pharm Biol 52:335–343

    Article  PubMed  Google Scholar 

  • Kim WJ, Kang HG, Kim SJ (2021) Dehydroabietic acid inhibits the gastric cancer cell growth via induced apoptosis and cell cycle arrest. Mol Cell Toxicol 17:133–139

    Article  CAS  Google Scholar 

  • Lheureux S, Braunstein M, Oza AM (2019a) Epithelial ovarian cancer: evolution of management in the era of precision medicine. CA Cancer J Clin 69:280–304

    PubMed  Google Scholar 

  • Lheureux S, Gourley C, Vergote I, Oza AM (2019b) Epithelial ovarian cancer. Lancet 393:1240–1253

    Article  PubMed  Google Scholar 

  • Linton MF, Moslehi JJ, Babaev VR (2019) Akt signaling in macrophage polarization, survival, and atherosclerosis. Int J Mol Sci 20

  • Lu Z, Xu S (2006) ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life 58:621–631

    Article  CAS  PubMed  Google Scholar 

  • Matulonis UA, Sood AK, Fallowfield L, Howitt BE, Sehouli J, Karlan BY (2016) Ovarian cancer. Nat Rev Dis Primers 2:16061

    Article  PubMed  PubMed Central  Google Scholar 

  • Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H (2019) Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health 11:287–299

    Article  PubMed  PubMed Central  Google Scholar 

  • Moussavou G, Kwak DH, Obiang-Obonou BW, Maranguy CA, Dinzouna-Boutamba SD, Lee DH, Pissibanganga OG, Ko K, Seo JI, Choo YK (2014) Anticancer effects of different seaweeds on human colon and breast cancers. Mar Drugs 12:4898–4911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Namvar F, Mohamad R, Baharara J, Zafar-Balanejad S, Fargahi F, Rahman HS (2013) Antioxidant, antiproliferative, and antiangiogenesis effects of polyphenol-rich seaweed (Sargassum muticum). Biomed Res Int 2013:604787

    Article  PubMed  PubMed Central  Google Scholar 

  • Ow YP, Green DR, Hao Z, Mak TW (2008) Cytochrome c: functions beyond respiration. Nat Rev Mol Cell Biol 9:532–542

    Article  CAS  PubMed  Google Scholar 

  • Prat J (2012) Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch 460:237–249

    Article  PubMed  Google Scholar 

  • Sanjeewa KKA, Lee JS, Kim WS, Jeon YJ (2017) The potential of brown-algae polysaccharides for the development of anticancer agents: An update on anticancer effects reported for fucoidan and laminaran. Carbohydr Polym 177:451–459

    Article  CAS  PubMed  Google Scholar 

  • Sui X, Kong N, Ye L, Han W, Zhou J, Zhang Q, He C, Pan H (2014) p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents. Cancer Lett 344:174–179

    Article  CAS  PubMed  Google Scholar 

  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 71:209–249

    Article  PubMed  Google Scholar 

  • Testa JR, Tsichlis PN (2005) AKT signaling in normal and malignant cells. Oncogene 24:7391–7393

    Article  CAS  PubMed  Google Scholar 

  • Torre LA, Siegel RL, Ward EM, Jemal A (2016) Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomarkers Prev 25:16–27

    Article  PubMed  Google Scholar 

  • Tournier C, Hess P, Yang DD, Xu J, Turner TK, Nimnual A, Bar-Sagi D, Jones SN, Flavell RA, Davis RJ (2000) Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 288:870–874

    Article  CAS  PubMed  Google Scholar 

  • Vyas S, Zaganjor E, Haigis MC (2016) Mitochondria and Cancer. Cell 166:555–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X (2019) Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer 18:26

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (grant number: 2021R1C1C1009807) and by the Technology Development Program (grant number: S3119951) funded by the Ministry of SMEs and Startups (MSS, Korea). We appreciate National Marine Biodiversity Institute of Korea (Seochun-gun, Chungchungnam-do, Korea) to provide Agarum clathratum extract.

Author information

Author notes

  1. Lihyun Kim and Taeyeon Hong contributed equally to this work.

Authors and Affiliations

  1. Department of Food and Nutrition, Kookmin University, Seoul, 02707, Republic of Korea

    Lihyun Kim

  2. Department of Biopharmaceutical Chemistry, Kookmin University, Seoul, 02707, Republic of Korea

    Lihyun Kim

  3. Department of Biological Sciences, Sungkyunkwan University, Suwon, 16419, Republic of Korea

    Taeyeon Hong & Whasun Lim

  4. Institute of Animal Molecular Biotechnology and Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, Republic of Korea

    Jiyeon Ham

Authors
  1. Lihyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Taeyeon Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiyeon Ham
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Whasun Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WL designed the study. LK and TH conducting experiments, analyzed the data, interpreted the data. WL provided reagents. LK and TH wrote the original draft of manuscript and WL and JH reviewed the draft of the manuscript. All authors have read and approved the manuscript.

Corresponding authors

Correspondence to Jiyeon Ham or Whasun Lim.

Ethics declarations

Conflict of interest

LK declares that she has no conflict of interest. TH declares that she has no conflict of interest. JH declares that she has no conflict of interest. WL declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, L., Hong, T., Ham, J. et al. Effects of Agarum clathratum extract on cell death and calcium ion levels of ovarian cancer cell. Mol. Cell. Toxicol. 19, 303–310 (2023). https://doi.org/10.1007/s13273-022-00259-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13273-022-00259-5

Keywords

Search

Navigation