Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF‑7 cells

  • Authors:
    • Huan Gao
    • Yue Zhang
    • Lei Dong
    • Xiao‑Yu Qu
    • Li‑Na Tao
    • Yue‑Ming Zhang
    • Jing‑Hui Zhai
    • Yan‑Qing Song
  • View Affiliations

  • Published online on: February 1, 2018     https://doi.org/10.3892/etm.2018.5830
  • Pages: 3413-3419
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

To investigate the effects of triptolide (TPI) on proliferation, autophagy and death in human breast cancer MCF‑7 cells, and to elucidate the associated molecular mechanisms, intracellular alterations were analyzed using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) and flow cytometry assays. The results of the MTT assay revealed that TPI significantly reduced the MCF‑7 cell survival rate when the concentration was >10 nmol/l. TPI activated a caspase cascade reaction by regulating Bcl‑2‑associated X protein (Bax), caspase‑3 and B‑cell lymphoma 2 expression, and promoted programmed cell death via the mitochondrial pathway. The results demonstrated that TPI significantly reduced the cell proliferation rate and viability in a time‑ and dose‑dependent manner, which was confirmed by western blotting and immunofluorescent staining. TPI induced autophagy and influenced p38 mitogen‑activated protein kinases, extracellular signal‑regulated kinase (Erk)1/2, and mammalian target of rapamycin (mTOR) phosphorylation, which resulted in apoptosis. When cells were treated with a combination of TPI and the Erk1/2 inhibitor U0126, the downregulation of P62 and upregulation of Bax were inhibited, which demonstrated that the inhibition of Erk1/2 reversed the autophagy changes induced by TPI. The results indicated that Erk1/2 activation may be a novel mechanism by which TPI induces autophagy and apoptosis in MCF‑7 breast cancer cells. In conclusion, TPI affects the proliferation and apoptosis of MCF‑7 cells, potentially via autophagy and p38/Erk/mTOR phosphorylation. The present study offers a novel view of the mechanisms by which TPI regulates cell death.
View Figures
View References

Related Articles

Journal Cover

April-2018
Volume 15 Issue 4

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Gao H, Zhang Y, Dong L, Qu XY, Tao LN, Zhang YM, Zhai JH and Song YQ: Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF‑7 cells. Exp Ther Med 15: 3413-3419, 2018.
APA
Gao, H., Zhang, Y., Dong, L., Qu, X., Tao, L., Zhang, Y. ... Song, Y. (2018). Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF‑7 cells. Experimental and Therapeutic Medicine, 15, 3413-3419. https://doi.org/10.3892/etm.2018.5830
MLA
Gao, H., Zhang, Y., Dong, L., Qu, X., Tao, L., Zhang, Y., Zhai, J., Song, Y."Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF‑7 cells". Experimental and Therapeutic Medicine 15.4 (2018): 3413-3419.
Chicago
Gao, H., Zhang, Y., Dong, L., Qu, X., Tao, L., Zhang, Y., Zhai, J., Song, Y."Triptolide induces autophagy and apoptosis through ERK activation in human breast cancer MCF‑7 cells". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3413-3419. https://doi.org/10.3892/etm.2018.5830