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Article

Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells

  • Authors:
    • Thressi Maxwell
    • Kyu Shik Lee
    • Soyoung Kim
    • Kyung-Soo Nam
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Medicine and Intractable Disease Research Center, Dongguk University, Gyeongju 38066, Republic of Korea
  • Pages: 1339-1349
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    Published online on: February 9, 2018
       https://doi.org/10.3892/ijo.2018.4271
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Abstract

Arctigenin, a member of the Asteraceae family, is a biologically active lignan that is consumed worldwide due to its several health benefits. However, its use may pose a problem for patients with estrogen receptor (ER)α-positive breast cancer, since studies have shown that arctigenin is a phytoestrogen that exerts a proliferative effect by binding to the ER. Thus, in this study, we examined the effect of arctigenin on ERα-positive MCF-7 human breast cancer cells to determine whether the consumption of arctigenin is safe for patients with breast cancer. First, we found that arctigenin inhibited the viability of the MCF-7 cells, and colony formation assay confirmed that this effect was cytotoxic rather than cytostatic. The cytotoxic effects were not mediated by cell cycle arrest, apoptosis, or necroptosis, despite DNA damage, as indicated by poly(ADP-ribose) polymerase (PARP) cleavage and phosphorylated H2A.X. An increase in lipidated LC3, a marker of autophagosome formation, was observed, indicating that autophagy was induced by arctigenin, which was found to be triggered by the inhibition of the mechanistic target of rapamycin (mTOR) pathway. We then examined the effects of arctigenin on ERα expression and determined whether it affects the sensitivity of the cells to tamoxifen, as tamoxifen is commonly used against hormone-responsive cancers and is known to act via the ERα. We found that treatment with arctigenin effectively downregulated ERα expression, which was found to be a consequence of the inhibition of the mTOR pathway. However, treatment with arctigenin in combination with tamoxifen did not affect the sensitivity of the cells to tamoxifen, but instead, exerted a synergistic effect. On the whole, our data indicate that the phytoestrogen, arctigenin, mainly targeted the mTOR pathway in ERα-positive MCF-7 human breast cancer cells, leading to autophagy-induced cell death and the downregulation of ERα expression. Furthermore, the synergistic effects between arctigenin and tamoxifen suggest that the consumption of arctigenin is not only safe for patients with hormone-sensitive cancers, but may also be an effective co-treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Maxwell T, Lee KS, Kim S and Nam K: Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells. Int J Oncol 52: 1339-1349, 2018.
APA
Maxwell, T., Lee, K.S., Kim, S., & Nam, K. (2018). Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells. International Journal of Oncology, 52, 1339-1349. https://doi.org/10.3892/ijo.2018.4271
MLA
Maxwell, T., Lee, K. S., Kim, S., Nam, K."Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells". International Journal of Oncology 52.4 (2018): 1339-1349.
Chicago
Maxwell, T., Lee, K. S., Kim, S., Nam, K."Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells". International Journal of Oncology 52, no. 4 (2018): 1339-1349. https://doi.org/10.3892/ijo.2018.4271
Copy and paste a formatted citation
x
Spandidos Publications style
Maxwell T, Lee KS, Kim S and Nam K: Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells. Int J Oncol 52: 1339-1349, 2018.
APA
Maxwell, T., Lee, K.S., Kim, S., & Nam, K. (2018). Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells. International Journal of Oncology, 52, 1339-1349. https://doi.org/10.3892/ijo.2018.4271
MLA
Maxwell, T., Lee, K. S., Kim, S., Nam, K."Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells". International Journal of Oncology 52.4 (2018): 1339-1349.
Chicago
Maxwell, T., Lee, K. S., Kim, S., Nam, K."Arctigenin inhibits the activation of the mTOR pathway, resulting in autophagic cell death and decreased ER expression in ER-positive human breast cancer cells". International Journal of Oncology 52, no. 4 (2018): 1339-1349. https://doi.org/10.3892/ijo.2018.4271
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