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Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway

  • Authors:
    • Jiahui Wei
    • Xuefeng Zhang
    • Huihao Pan
    • Song He
    • Bao Yuan
    • Qing Liu
    • Jiabao Zhang
    • Yu Ding
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin 130062, P.R. China, College of Animal Science and Technology, Jilin Agricultural University, Changchun, Jilin 130118, P.R. China, The Second Clinical School of Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine‑Zhuhai Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 332
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    Published online on: February 25, 2021
       https://doi.org/10.3892/ol.2021.12593
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Abstract

Eupafolin is a flavonoid extracted from common sage. Previous studies have reported that Eupafolin has antioxidant, anti‑inflammatory, and anti‑tumor effects. However, its role in breast cancer remains unclear. The present study investigated the effects and underlying mechanism of action of Eupafolin using breast cancer cell lines. The effects of Eupafolin on breast cancer cell proliferation, migration, apoptosis and the cell cycle were determined. Cell viability and Transwell assays, reverse transcription‑quantitative PCR, flow cytometry and western blot analysis were used in this study. The data showed that the proliferation, migration and invasion ability of EO771 cells treated with Eupafolin was significantly decreased, and the apoptosis rate was increased compared with that of the control. The protein levels of Bax and cleaved caspase 3 increased, whereas that of Bcl‑2 decreased. In addition, Eupafolin treatment also caused the proliferation of breast cancer cells to be arrested at the G0/G1 phase. Furthermore, results from western blotting indicated that Eupafolin treatment decreased the protein levels of p‑PI3K, p‑Akt and p‑mTOR. Taken together, the present findings demonstrate that Eupafolin has a significant inhibitory effect on the proliferation of EO771 cells, inhibits cell migration and invasion, and promotes cell apoptosis, thereby causing G0/G1 phase arrest, at least partially through the PI3K/Akt/mTOR signaling pathway. Therefore, the findings provide novel insights regarding the use of Eupafolin for the treatment of breast cancer.
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View References

1 

Watkins EJ: Overview of breast cancer. JAAPA. 32:13–17. 2019. View Article : Google Scholar : PubMed/NCBI

2 

Gao W, Ge S and Sun J: Ailanthone exerts anticancer effect by up-regulating miR-148a expression in MDA-MB-231 breast cancer cells and inhibiting proliferation, migration and invasion. Biomed Pharmacother. 109:1062–1069. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Chung KS, Choi JH, Back NI, Choi MS, Kang EK, Chung HG, Jeong TS and Lee KT: Eupafolin, a flavonoid isolated from Artemisia princeps, induced apoptosis in human cervical adenocarcinoma HeLa cells. Mol Nutr Food Res. 54:1318–1328. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Jiang H, Wu D, Xu D, Yu H, Zhao Z, Ma D and Jin J: Eupafolin exhibits potent anti-angiogenic and antitumor activity in hepatocellular carcinoma. Int J Biol Sci. 13:701–711. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Fan X, Tao J, Cai Z, Fredimoses M, Wu J, Jiang Z, Zhang K and Li S: Eupafolin suppresses esophagus cancer growth by targeting T-LAK cell-originated protein kinase. Front Pharmacol. 10:12482019. View Article : Google Scholar : PubMed/NCBI

6 

Liu K, Park C, Chen H, Hwang J, Thimmegowda NR, Bae EY, Lee KW, Kim HG, Liu H, Soung NK, et al: Eupafolin suppresses prostate cancer by targeting phosphatidylinositol 3-kinase-mediated Akt signaling. Mol Carcinog. 54:751–760. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Am JU, Gong WJ, Su Y and Mou ZB: Imperatorin shows selective antitumor effects in SGC-7901 human gastric adenocarcinoma cells by inducing apoptosis, cell cycle arrest and targeting PI3K/Akt/m-TOR signalling pathway. J BUON. 22:1471–1476. 2017.PubMed/NCBI

8 

Zhang Y, Zhang R and Ni H: Eriodictyol exerts potent anticancer activity against A549 human lung cancer cell line by inducing mitochondrial-mediated apoptosis, G2/M cell cycle arrest and inhibition of m-TOR/PI3K/Akt signalling pathway. Arch Med Sci. 16:446–452. 2019. View Article : Google Scholar : PubMed/NCBI

9 

Zhao JG, Zhang L, Xiang XJ, Yu F, Ye WL, Wu DP, Wang JF and Xiong JP: Amarogentin secoiridoid inhibits in vivo cancer cell growth in xenograft mice model and induces apoptosis in human gastric cancer cells (SNU-16) through G2/M cell cycle arrest and PI3K/Akt signalling pathway. J BUON. 21:609–617. 2016.PubMed/NCBI

10 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Thorat MA and Balasubramanian R: Breast cancer prevention in high-risk women. Best Pract Res Clin Obstet Gynaecol. 65:18–31. 2020. View Article : Google Scholar : PubMed/NCBI

12 

Zhang XQ, Yao C, Bian WH, Chen X, Xue JX, Zhu ZY, Ying Y, Xu YL and Wang C: Effects of Astragaloside IV on treatment of breast cancer cells execute possibly through regulation of Nrf2 via PI3K/AKT/mTOR signaling pathway. Food Sci Nutr. 7:3403–3413. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Lai ZR, Ho YL, Huang SC, Huang TH, Lai SC, Tsai JC, Wang CY, Huang GJ and Chang YS: Antioxidant, anti-inflammatory and antiproliferative activities of Kalanchoe gracilis (L.) DC Stem. Am J Chin Med. 39:1275–1290. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Han MA, Min KJ, Woo SM, Seo BR and Kwon TK: Eupafolin enhances TRAIL-mediated apoptosis through cathepsin S-induced down-regulation of Mcl-1 expression and AMPK-mediated Bim up-regulation in renal carcinoma Caki cells. Oncotarget. 7:65707–65720. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Wang X, Hu Z, Wang Z, Cui Y and Cui X: Angiopoietin-like protein 2 is an important facilitator of tumor proliferation, metastasis, angiogenesis and glycolysis in osteosarcoma. Am J Transl Res. 11:6341–6355. 2019.PubMed/NCBI

16 

Aksenenko MB, Palkina NV, Sergeeva ON, Yu Sergeeva E, Kiriehenko AK and Ruksha TG: miR-155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16-bearing mice at the premetastatic stage. Int J Exp Pathol. 100:311–319. 2019. View Article : Google Scholar : PubMed/NCBI

17 

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

18 

Zeng C, Ke Z, Song Y, Yao Y, Hu X, Zhang M, Li H and Yin J: Annexin A3 is associated with a poor prognosis in breast cancer and participates in the modulation of apoptosis in vitro by affecting the Bcl-2/Bax balance. Exp Mol Pathol. 95:23–31. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Cao Z, Zhang G, Xie C and Zhou Y: miR-34b regulates cervical cancer cell proliferation and apoptosis. Artif Cells Nanomed Biotechnol. 47:2042–2047. 2019. View Article : Google Scholar : PubMed/NCBI

20 

Liu R, Chen Y, Shou T, Hu J, Chen J and Qing C: TRIM67 promotes NFκB pathway and cell apoptosis in GA-13315-treated lung cancer cells. Mol Med Rep. 20:2936–2944. 2019.PubMed/NCBI

21 

Wu G, Zheng H, Xu J, Guo Y, Zheng G, Ma C, Hao S, Liu X, Chen H, Wei S, et al: miR-429 suppresses cell growth and induces apoptosis of human thyroid cancer cell by targeting ZEB1. Artif Cells Nanomed Biotechnol. 47:548–554. 2019. View Article : Google Scholar : PubMed/NCBI

22 

Zhou J, Xia L and Zhang Y: Naringin inhibits thyroid cancer cell proliferation and induces cell apoptosis through repressing PI3K/AKT pathway. Pathol Res Pract. 215:1527072019. View Article : Google Scholar : PubMed/NCBI

23 

Qiu J, Zhang T, Zhu X, Yang C, Wang Y, Zhou N, Ju B, Zhou T, Deng G and Qiu C: Hyperoside induces breast cancer cells apoptosis via ROS-Mediated NF-κB signaling pathway. Int J Mol Sci. 21:1312019. View Article : Google Scholar

24 

Noori S and Hassan ZM: Tehranolide inhibits proliferation of MCF-7 human breast cancer cells by inducing G0/G1 arrest and apoptosis. Free Radic Biol Med. 52:1987–1999. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Suryavanshi S, Choudhari A, Raina P and Kaul-Ghanekar R: A polyherbal formulation, HC9 regulated cell growth and expression of cell cycle and chromatin modulatory proteins in breast cancer cell lines. J Ethnopharmacol. 242:1120222019. View Article : Google Scholar : PubMed/NCBI

26 

Ahn H, Im E, Lee DY, Lee HJ, Jung JH and Kim SH: Antitumor Effect of pyrogallol via miR-134 mediated S phase arrest and inhibition of PI3K/AKT/Skp2/cMyc signaling in hepatocellular carcinoma. Int J Mol Sci. 20:39852019. View Article : Google Scholar

27 

Hunter T and Pines J: Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 79:573–582. 1994. View Article : Google Scholar : PubMed/NCBI

28 

Park W, Park S, Song G and Lim W: Inhibitory effects of osthole on human breast cancer cell progression via induction of cell cycle arrest, mitochondrial dysfunction, and ER stress. Nutrients. 11:27772019. View Article : Google Scholar

29 

Gao X, Wang Y, Li Y, Wang Y, Yan M, Sun H, Chen S and Pan X: Huganpian, a traditional Chinese medicine, inhibits liver cancer growth in vitro and in vivo by inducing autophagy and cell cycle arrest. Biomed Pharmacother. 120:1094692019. View Article : Google Scholar : PubMed/NCBI

30 

Liu X, Sun L, Zhang S, Zhang S and Li W: GINS2 facilitates epithelial-to-mesenchymal transition in non-small-cell lung cancer through modulating PI3K/Akt and MEK/ERK signaling. J Cell Physiol. 235:7747–7756. 2020. View Article : Google Scholar : PubMed/NCBI

31 

Guo L and Yang T: Oxymatrine inhibits the proliferation and invasion of breast cancer cells via the PI3K pathway. Cancer Manag Res. 11:10499–10508. 2019. View Article : Google Scholar : PubMed/NCBI

32 

Murugan AK: Special issue: PI3K/Akt signaling in human cancer. Semin Cancer Biol. 59:1–2. 2019. View Article : Google Scholar : PubMed/NCBI

33 

Zhang J, Qu Z, Yao H, Sun L, Harata-Lee Y, Cui J, Aung TN, Liu X, You R, Wang W, et al: An effective drug sensitizing agent increases gefitinib treatment by down regulating PI3K/Akt/mTOR pathway and up regulating autophagy in non-small cell lung cancer. Biomed Pharmacother. 118:1091692019. View Article : Google Scholar : PubMed/NCBI

34 

Shi N, Yu H and Chen T: Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway. Onco Targets Ther. 12:7637–7647. 2019. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wei J, Zhang X, Pan H, He S, Yuan B, Liu Q, Zhang J and Ding Y: Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway. Oncol Lett 21: 332, 2021.
APA
Wei, J., Zhang, X., Pan, H., He, S., Yuan, B., Liu, Q. ... Ding, Y. (2021). Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway. Oncology Letters, 21, 332. https://doi.org/10.3892/ol.2021.12593
MLA
Wei, J., Zhang, X., Pan, H., He, S., Yuan, B., Liu, Q., Zhang, J., Ding, Y."Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway". Oncology Letters 21.4 (2021): 332.
Chicago
Wei, J., Zhang, X., Pan, H., He, S., Yuan, B., Liu, Q., Zhang, J., Ding, Y."Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway". Oncology Letters 21, no. 4 (2021): 332. https://doi.org/10.3892/ol.2021.12593
Copy and paste a formatted citation
x
Spandidos Publications style
Wei J, Zhang X, Pan H, He S, Yuan B, Liu Q, Zhang J and Ding Y: Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway. Oncol Lett 21: 332, 2021.
APA
Wei, J., Zhang, X., Pan, H., He, S., Yuan, B., Liu, Q. ... Ding, Y. (2021). Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway. Oncology Letters, 21, 332. https://doi.org/10.3892/ol.2021.12593
MLA
Wei, J., Zhang, X., Pan, H., He, S., Yuan, B., Liu, Q., Zhang, J., Ding, Y."Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway". Oncology Letters 21.4 (2021): 332.
Chicago
Wei, J., Zhang, X., Pan, H., He, S., Yuan, B., Liu, Q., Zhang, J., Ding, Y."Eupafolin inhibits breast cancer cell proliferation and induces apoptosis by inhibiting the PI3K/Akt/mTOR pathway". Oncology Letters 21, no. 4 (2021): 332. https://doi.org/10.3892/ol.2021.12593
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