The effects of Sideritis akmanii on endoplasmic reticulum stress, inflammation, and DNA damage in experimentally ER-stress-induced MCF-7 cancer cells

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MCF-7, ER-stress, Comet assay, Sideritis akmanii, Cytotoxicity, Genotoxicity


Cancer is one of the diseases that became a social problem that can happen with uncontrolled proliferation, growth, differentiation, and spread of cells in our body. Breast cancer, on the other hand, is one of the types of cancer with the highest incidence in women. In our study, endoplasmic reticulum (ER) stress is induced by thapsigargin (T) in MCF-7 cells and then, the effects of Sideritis akmanii acetone extract (SAE) on cell viability, ER stress, inflammation, and DNA damage were investigated. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test was used to determine the effect of SAE on cytotoxicity and the comet (SCGE; single-cell gel electrophoresis) assay was used for the effects on genotoxicity. Additionally, the mRNA expression levels of both ER stress parameters (ATF4: activating transcription factor 4, ATF6: activating transcription factor 6, PERK: protein kinase RNA-like ER kinase, GRP78: glucose-regulated protein 78) and inflammation-related parameters (TNF alpha: tumor necrosis factor-alpha, IFN-gamma: interferon-gamma, IL-6: interleukin-6, IL-8: interleukin-8, IL-12: interleukin-12) were determined by qPCR. The results showed that DNA damage levels increased as a result of T treatment, DNA damage caused by T decreased when a low dose of SAE was administered and a high dose of SAE further increased DNA damage levels. It was determined that SAE, administered in different doses with T or alone in experimental groups, increased mRNA expression levels of all ER stress and inflammatory genes compared to the control group. As a result, it has been determined that S. akmanii, especially at high doses, may exhibit anticarcinogenic effects through its effects on genotoxic, cytotoxic, and ER stress in MCF-7 cells.


Christen, V., & Fent, K. (2016). Silica nanoparticles induce endoplasmic reticulum stress response and activate mitogen activated kinase (MAPK) signalling. Toxicology Reports, 3, 832-840.

Çelik, S., Serkan, S., & Hazman, Ö. (2015). Endoplasmik retikulum stresine cevap yolakları ve tip 2 diyabet patogenezinde endoplasmik retikulum stres aracılı beta hücre apoptosisinin rolü. Kocatepe Tıp Dergisi, 16(3), 227-237.

Das, A., Majumder, D., & Saha, C. (2017). Correlation of binding efficacies of DNA to flavonoids and their induced cellular damage. Journal of Photochemistry and Photobiology B: Biology, 170, 256-262.

Evyapan, G., Ay, G., Cömertpay, G., & Luleyap, H. (2019). Role of endoplasmic reticulum stress response in tumorogenesis. Cukurova Medical Journal, 44(1), 241-248.

Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer, 136(5), E359-E386.

Fribley, A., Zhang, K., & Kaufman, R. J. (2009). Regulation of apoptosis by the unfolded protein response. In Apoptosis (pp. 191-204): Springer.

Guo, Y. X., Lin, Z. M., Wang, M. J., Dong, Y. W., Niu, H. M., Young, C. Y., Lou, H. X., & Yuan, H. Q. (2016). Jungermannenone A and B induce ROS-and cell cycle-dependent apoptosis in prostate cancer cells in vitro. Acta Pharmacologica Sinica, 37(6), 814-824.

Günay, E., Celik, S., Sarinc-Ulasli, S., Özyürek, A., Hazman, Ö., Günay, S., Özdemir, M., & Ünlü, M. (2016). Comparison of the anti-inflammatory effects of proanthocyanidin, quercetin, and damnacanthal on benzo (a) pyrene exposed A549 alveolar cell line. Inflammation, 39(2), 744-751.

Hazman, Ö., Bozkurt, M. F., Fidan, A. F., Uysal, F. E., & Çelik, S. (2018). The effect of boric acid and borax on oxidative stress, inflammation, ER stress and apoptosis in cisplatin toxication and nephrotoxicity developing as a result of toxication. Inflammation, 41(3), 1032-1048.

Hazman, Ö., Sarıova, A., Bozkurt, M. F., & Ciğerci, İ. H. (2021). The anticarcinogen activity of β-arbutin on MCF-7 cells: Stimulation of apoptosis through estrogen receptor-α signal pathway, inflammation and genotoxicity. Molecular and Cellular Biochemistry, 476(1), 349-360.

Imai, T., Kosuge, Y., Saito, H., Uchiyama, T., Wada, T., Shimba, S., Ishige, K., Miyairi, S., Makishima, M., et al. (2016). Neuroprotective effect of S-allyl-l-cysteine derivatives against endoplasmic reticulum stress-induced cytotoxicity is independent of calpain inhibition. Journal of Pharmacological Sciences, 130(3), 185-188.

Kapuy, O., Vinod, P., & Bánhegyi, G. (2014). mTOR inhibition increases cell viability via autophagy induction during endoplasmic reticulum stress–An experimental and modeling study. FEBS Open Bio, 4, 704-713.

Kogiannou, D. A., Kalogeropoulos, N., Kefalas, P., Polissiou, M. G., & Kaliora, A. C. (2013). Herbal infusions; their phenolic profile, antioxidant and anti-inflammatory effects in HT29 and PC3 cells. Food and Chemical Toxicology, 61, 152-159.

Loizzo, M. R., Tundis, R., Menichini, F., Saab, A. M., Statti, G. A., & Menichini, F. (2007). Cytotoxic activity of essential oils from Labiatae and Lauraceae families against in vitro human tumor models. Anticancer Research, 27(5A), 3293-3299.

McPherson, K., Steel, C., & Dixon, J. (2000). Breast cancer—epidemiology, risk factors, and genetics. British Medical Journal, 321(7261), 624-628.

Mori, K. (2000). Tripartite management of unfolded proteins in the endoplasmic reticulum. Cell, 101(5), 451-454.

Pfaffle, M. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research, 29, 2002-2007.

Samadi, A. K., Bilsland, A., Georgakilas, A. G., Amedei, A., Amin, A., Bishayee, A., Azmi, A. S., Lokeshwar, B. L., Grue, B., et al. (2015). A multi-targeted approach to suppress tumor-promoting inflammation. Paper presented at the Seminars in Cancer Biology.

Sancho-Martínez, S. M., Prieto-García, L., Prieto, M., Lopez-Novoa, J. M., & López-Hernández, F. J. (2012). Subcellular targets of cisplatin cytotoxicity: an integrated view. Pharmacology & Therapeutics, 136(1), 35-55.

Singh, N. P., McCoy, M. T., Tice, R. R., & Schneider, E. L. (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Experimental Cell Research, 175(1), 184-191.

Sozen, E., & Ozer, N. K. (2017). Impact of high cholesterol and endoplasmic reticulum stress on metabolic diseases: An updated mini-review. Redox Biology, 12, 456-461.

Tice, R. R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., Miyamae, Y., Rojas, E., Ryu, J. C., et al. (2000). Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environmental and Molecular Mutagenesis, 35(3), 206-221.

Todorova, M., & Trendafilova, A. (2014). Sideritis scardica Griseb., an endemic species of Balkan peninsula: Traditional uses, cultivation, chemical composition, biological activity. Journal of Ethnopharmacology, 152(2), 256-265.

Treiman, M. (2002). Regulation of the endoplasmic reticulum calcium storage during the unfolded protein response—significance in tissue ischemia? Trends in Cardiovascular Medicine, 12(2), 57-62.

Ulasli, S. S., Celik, S., Gunay, E., Ozdemir, M., Hazman, O., Ozyurek, A., Koyuncu, T., & Unlu, M. (2013). Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo (a) pyrene. Asian Pacific Journal of Cancer Prevention, 14(10), 6159-6164.

Yumrutas, O., Oztuzcu, S., Pehlivan, M., Ozturk, N., Poyraz, I. E., Igci, Y. Z., Cevik, M. O., Bozgeyik, I., Aksoy, A. F., et al. (2015). Cell viability, anti-proliferation and antioxidant activities of Sideritis syriaca, Tanacetum argenteum sub sp. argenteum and Achillea aleppica subsp. zederbaueri on human breast cancer cell line (MCF-7). Journal of Applied Pharmaceutical Science, 5(3), 1-5.

Zhou, Y., Shu, F., Liang, X., Chang, H., Shi, L., Peng, X., Zhu, J., & Mi, M. (2014). Ampelopsin induces cell growth inhibition and apoptosis in breast cancer cells through ROS generation and endoplasmic reticulum stress pathway. PLoS ONE, 9(2), e89021.




How to Cite

Cigerci, I. H., Turhan, H., Hazman, O., & Isitez, N. (2022). The effects of Sideritis akmanii on endoplasmic reticulum stress, inflammation, and DNA damage in experimentally ER-stress-induced MCF-7 cancer cells. International Journal of Plant Based Pharmaceuticals, 3(1), 47–53.



Research Articles
Received 2022-09-26
Accepted 2022-11-06
Published 2022-11-08