Skip to main content
Log in

Jasmonic Acid Induces Endoplasmic Reticulum Stress with Different Outcome in Cultured Normal and Tumor Epidermal Cells

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Plant hormones produce cytotoxic effect on human cells and can trigger the processes unrelated to cell death, e.g., biosynthetic system stress. The goal of this study was to investigate activation of the endoplasmic reticulum (ER) stress by jasmonic acid (JA) and to distinguish between the responses of cultured immortalized non-tumorigenic HaCaT cells and epidermoid carcinoma A431 cells to this plant hormone. JA was used in the concentration of 2 mM, as it suppressed cell proliferation in both cell lines. We analyzed expression of genes associated with the activation of ER stress (GRP78, ATF4, CHOP), the structure of the ER and Golgi complex, and synthetic processes in the HaCaT and A431 cell lines. JA induced expression of genes responsible for the activation of ER stress and caused hypertrophic changes in the Golgi complex in both cell lines. However, the patterns of gene expression in the HaCaT and A431 cells were different, and higher levels of involucrin synthesis were observed in A431 but not in HaCaT cells, suggesting that JA activated differentiation of the tumor A431 cells only. Therefore, JA induced ER stress in both cell lines, but the consequences of ER stress were different for the epidermal immortalized non-tumorigenic and tumor cells.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

DAPI:

4,6-diamidino-2-phenylindole hydrochlorid

DMSO:

dimethyl sulfoxide

DTT:

dithiothreitol

ER:

endoplasmic reticulum

JA:

jasmonic acid

qPCR:

real-time polymerase chain reaction

PI:

propidium iodide

TEM:

transmission electron microscopy

TGN:

trans-Golgi network

UPR:

unfolded protein response

References

  1. Wasternack, C., and Hause, B. (2013) Jasmonates: biosynthesis, perception, signal transduction and action in plant stress response, growth and development. An update to the 2007 review in Annals of Botany, Ann. Bot., 111, 1021–1058, doi: doi: https://doi.org/10.1093/aob/mct067.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Song, S., Qi, T., Wasternack, C., and Xie, D. (2014) Jasmonate signaling and crosstalk with gibberellin and ethylene, Curr. Opin. Plant Biol., 21, 112–119, doi: https://doi.org/10.1016/j.pbi.2014.07.005..

    Article  CAS  PubMed  Google Scholar 

  3. Fingrut, O., and Flescher, E. (2002) Plant stress hormones suppress the proliferation and induce apoptosis in human cancer cells, Leukemia, 16, 608–616, doi: https://doi.org/10.1038/sj.leu.2402419..

    Article  CAS  PubMed  Google Scholar 

  4. Rotem, R., Heyfets, A., Fingrut, O., Blickstein, D., Shaklai, M., and Flescher, E. (2005) Jasmonates: novel anticancer agents acting directly and selectively on human cancer cell mitochondria, Cancer Res., 65, 1984–1993, doi: https://doi.org/10.1158/0008-5472.CAN-04-3091..

    Article  CAS  PubMed  Google Scholar 

  5. Li, J., Chen, K., Wang, F., Dai, W., Li, S., Feng, J., Wu, L., Liu, T., Xu, S., Xia, Y., Lu, J., Zhou, Y., Xu, L., and Guo, C. (2017) Methyl jasmonate leads to necrosis and apoptosis in hepatocellular carcinoma cells via inhibition of glycolysis and represses tumor growth in mice, Oncotarget, 8, 45965–45980, doi: https://doi.org/10.18632/oncotarget.17469..

    PubMed  PubMed Central  Google Scholar 

  6. Henriet, E., Jager, S., Tran, C., Bastien, P., Michelet, J. F., Minondo, A. M., Formanek, F., Dalko-Csiba, M., Lortat-Jacob, H., Breton, L., and Vives, R. R. (2017) A jasmonic acid derivative improves skin healing and induces changes in proteoglycan expression and glycosaminoglycan structure, Biochim. Biophys. Acta Gen. Subj., 1861, 2250–2260, doi: https://doi.org/10.1016/j.bbagen.2017.06.006..

    Article  CAS  PubMed  Google Scholar 

  7. Tsumura, H., Akimoto, M., Kiyota, H., Ishii, Y., Ishikura, H., and Honma, Y. (2009) Gene expression profiles in differentiating leukemia cells induced by methyl jasmonate are similar to those of cytokinins and methyl jasmonate analogs induce the differentiation of human leukemia cells in primary culture, Leukemia, 23, 753–760, doi: https://doi.org/10.1038/leu.2008.347..

    Article  CAS  PubMed  Google Scholar 

  8. Vildanova, M. S., Savitskaya, M. A., Onishchenko, G. E., and Smirnova, E. A. (2014) Effect of plant hormones on components of the secretory pathway of normal and tumor human cells, Tsitologiya, 56, 516–525.

    CAS  Google Scholar 

  9. Fu, J., Zhao, L., Wang, L., and Zhu, X. (2015) Expression of markers of endoplasmic reticulum stress-induced apoptosis in the placenta of women with early and late onset severe pre-eclampsia, Taiwan J. Obstet. Gynecol., 54, 19–23, doi: https://doi.org/10.1016/j.tjog.2014.11.002..

    Article  PubMed  Google Scholar 

  10. Murugan, D., Lau, Y. S., Lau, C. W., Mustafa, M. R., and Huang, Y. (2015) Angiotensin 1–7 protects against angiotensin II-induced endoplasmic reticulum stress and endothelial dysfunction via Mas receptor, PLoS One, 10, e0145413, doi: https://doi.org/10.1371/journal.pone.0145413..

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Plaisance, V., Brajkovic, S., Tenenbaum, M., Favre, D., Ezanno, H., Bonnefond, A., Bonner, C., Gmyr, V., Kerr-Conte, J., Gauthier, B. R., Widmann, C., Waeber, G., Pattou, F., Froguel, P., and Abderrahmani, A. (2016) Endoplasmic reticulum stress links oxidative stress to impaired pancreatic β-cell function caused by human oxdized LDL, PLoS One, 11, e0163046, doi: https://doi.org/10.1371/journal.pone.0163046..

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Vandesompele, J., De Preter, K., Pattyn, F., Poppe, B., Van Roy, N., De Paepe, A., and Speleman, F. (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes, Genome Biol., 3, doi: https://doi.org/10.1186/gb-2002-3-7-research0034.

  13. Potashnikova, D., Gladkikh, A., and Vorobjev, I. A. (2015) Selection of superior reference genes’ combination for quantitative real-time PCR in B-cell lymphomas, Ann. Clin. Lab. Sci., 45, 64–72.

    CAS  PubMed  Google Scholar 

  14. Reynolds, E. S. (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy, J. Cell Biol., 17, 208–212, doi: https://doi.org/10.1083/jcb.17.1.208..

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Mishra, A. R., Zheng, J., Tang, X., and Goering, P. L. (2016) Silver nanoparticle-induced autophagic-lysosomal disruption and NLRP3-inflammasome activation in HepG2 cells is size-dependent, Toxicol. Sci., 150, 473–487, doi: https://doi.org/10.1093/toxsci/kfw011..

    Article  CAS  PubMed  Google Scholar 

  16. Smith, M., and Wilkinson, S. (2017) ER homeostasis and autophagy, Essays Biochem., 61, 625–635, doi: https://doi.org/10.1042/EBC20170092..

    Article  PubMed  PubMed Central  Google Scholar 

  17. Matsuzaki, S., Hiratsuka, T., Taniguchi, M., Shingaki, K., Kubo, T., Kiya, K., Fujiwara, T., Kanazawa, S., Kanematsu, R., Maeda, T., Takamura, H., Yamada, K., Miyoshi, K., Hosokawa, K., Tohyama, M., and Katayama, T. (2015) Physiological ER stress mediates the differentiation of fibroblasts, PLoS One, 10, e0123578, doi: https://doi.org/10.1371/journal.pone.0123578..

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Sugiura, K. (2013) Unfolded protein response in keratinocytes: impact on normal and abnormal keratinization, J. Dermatol. Sci., 69, 181–186, doi: https://doi.org/10.1016/j.jdermsci.2012.12.002..

    Article  CAS  PubMed  Google Scholar 

  19. Chakrabarti, A., Chen, A. W., and Varner, J. D. (2011) A review of the mammalian unfolded protein response, Biotechnol. Bioeng., 108, 2777–2793, doi: https://doi.org/10.1002/bit.23282..

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rozpedek, W., Pytel, D., Mucha, B., Leszczynska, H., Diehl, J. A., and Majsterek, I. (2016) The role of the PERK/eIF2α/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress, Curr. Mol. Med., 16, 533–544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Celli, A., Mackenzie, D. S., Crumrine, D. S., Tu, C. L., Hupe, M., Bikle, D. D., Elias, P. M., and Mauro, T. M. (2011) Endoplasmic reticulum Ca2+ depletion activates XBP1 and controls terminal differentiation in keratinocytes and epidermis, Br. J. Dermatol., 164, 16–25, doi: https://doi.org/10.1111/j.1365-2133.2010.10046.x..

    Article  CAS  PubMed  Google Scholar 

  22. Eckhart, L., Lippens, S., Tschachler, E., and Declercq, W. (2013) Cell death by cornification, Biochim. Biophys. Acta, 1833, 3471–3480, doi: https://doi.org/10.1016/j.bbamcr.2013.06.010..

    Article  CAS  PubMed  Google Scholar 

  23. Rosdy, M., Bernard, B. A., Schmidt, R., and Darmon, M. (1986) Incomplete epidermal differentiation of A431 epidermoid carcinoma cells, In vitro Cell Dev. Biol., 22, 295–300.

    Article  CAS  PubMed  Google Scholar 

  24. Yamazaki, T., Nakano, H., Hayakari, M., Tanaka, M., Mayama, J., and Tsuchida, S. (2004) Differentiation induction of human keratinocytes by phosphatidylethanolamine-binding protein, J. Biol. Chem., 279, 32191–32195, doi: https://doi.org/10.1074/jbc.M404029200..

    Article  CAS  PubMed  Google Scholar 

  25. Huang, C.-S., Ho, W.-L., Lee, W.-S., Sheu, M.-T., Wang, Y.-J., Tu, S.-H., Chen, R.-J., Chu, J.-S., Chen, L.-C., Lee, C.-H., Tseng, H., Ho, Y.-S., and Wu, C.-H. (2008) SP1-regulated p27/Kip1 gene expression is involved in terbinafine-induced human A431 cancer cell differentiation: an in vitro and in vivo study, Biochem. Pharmacol., 75, 1783–1796, doi: https://doi.org/10.1016/j.bcp.2008.02.005..

    Article  CAS  PubMed  Google Scholar 

  26. Eckert, R. L., Crish, J. F., Efimova, T., and Balasubramanian, S. (2004) Antioxidants regulate normal human keratinocyte differentiation, Biochem. Pharmacol., 68, 1125–1131, doi: https://doi.org/10.1016/j.bcp.2004.04.029..

    Article  CAS  PubMed  Google Scholar 

  27. Cohen, S., and Flescher, E. (2009) Methyl jasmonate: a plant stress hormone as an anti-cancer drug, Phytochemistry, 70, 1600–1609, doi: https://doi.org/10.1016/j.phytochem.2009.06.007..

    Article  CAS  PubMed  Google Scholar 

  28. Rotem, R., Fingrut, O., Moskovitz, J., and Flescher, E. (2003) The anti-cancer plant stress-protein methyl jas-monate induces activation of stress-regulated c-Jun N-ter-minal kinase and p38 protein kinase in human lymphoid cells, Leukemia, 17, 2230–2234, doi: https://doi.org/10.1038/sj.leu.2403107..

    Article  CAS  PubMed  Google Scholar 

  29. Xiang, X. Y., Yang, X. C., Su, J., Kang, J. S., Wu, Y., Xue, Y. N., Dong, Y. T., and Sun, L. K. (2016) Inhibition of autophagic flux by ROS promotes apoptosis during DTT-induced ER/oxidative stress in HeLa cells, Oncol. Rep., 35, 3471–3479, doi: https://doi.org/10.3892/or.2016.4725..

    Article  CAS  PubMed  Google Scholar 

  30. Liang, S. H., Zhang, W., McGrath, B. C., Zhang, P., and Cavener, D. R. (2006) PERK (eIF2α kinase) is required to activate the stress-activated MAPKs and induce the expression of immediate-early genes upon disruption of ER calcium homoeostasis, Biochem. J., 393, 201–209, doi: https://doi.org/10.1042/BJ20050374.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Funding. The work was supported by the Russian Foundation for Basic Research (project 19-015-00233) and the Development Program of the Moscow State University (complex FACSAria SORP).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. S. Vildanova.

Ethics declarations

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

Additional information

Conflict of interest. The authors declare no conflict of interest.

Russian Text © The Author(s), 2019, published in Biokhimiya, 2019, Vol. 84, No. 9, pp. 1289–1300.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19-088, August 5, 2019.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vildanova, M.S., Saidova, A.A., Fokin, A.I. et al. Jasmonic Acid Induces Endoplasmic Reticulum Stress with Different Outcome in Cultured Normal and Tumor Epidermal Cells. Biochemistry Moscow 84, 1047–1056 (2019). https://doi.org/10.1134/S0006297919090074

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297919090074

Keywords

Navigation