Triptolide induces apoptosis through the calcium/calmodulin‑dependent protein kinase kinaseβ/AMP‑activated protein kinase signaling pathway in non‑small cell lung cancer cells

  • Authors:
    • Tao Ren
    • Yi‑Jun Tang
    • Mei‑Fang Wang
    • Han‑Sheng Wang
    • Yan Liu
    • Xin Qian
    • Chan Chang
    • Ming‑Wei Chen
  • View Affiliations

  • Published online on: September 11, 2020     https://doi.org/10.3892/or.2020.7763
  • Pages: 2288-2296
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Abstract

Triptolide, a triterpene extracted from the Chinese herb Tripterygium wilfordii, has been reported to exert multiple bioactivities, including immunosuppressive, anti‑inflammatory and anticancer effects. Although the anticancer effect of triptolide has attracted significant attention, the specific anticancer mechanism in non‑small‑cell lung cancer (NSCLC) remains unclear. The present study aimed to investigate the anticancer effect of triptolide in the H1395 NSCLC cell line and to determine its mechanism of action. The results revealed that triptolide significantly inhibited the cell viability of NSCLC cells in a dose‑dependent manner, which was suggested to be through inducing apoptosis. In addition, triptolide was revealed to activate the calcium (Ca2+)/calmodulin‑dependent protein kinase kinase β (CaMKKβ)/AMP‑activated protein kinase (AMPK) signaling pathway by regulating the intracellular Ca2+ concentration levels, which increased the phosphorylation levels of AMPK and reduced the phosphorylation levels of AKT, ultimately leading to apoptosis. The CaMKKβ blocker STO‑609 and the AMPK blocker Compound C significantly inhibited the apoptosis‑promoting effect of triptolide. In conclusion, the results of the present study suggested that triptolide may induce apoptosis through the CaMKKβ‑AMPK signaling pathway and may be a promising drug for the treatment of NSCLC.
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November-2020
Volume 44 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ren T, Tang YJ, Wang MF, Wang HS, Liu Y, Qian X, Chang C and Chen MW: Triptolide induces apoptosis through the calcium/calmodulin‑dependent protein kinase kinaseβ/AMP‑activated protein kinase signaling pathway in non‑small cell lung cancer cells. Oncol Rep 44: 2288-2296, 2020
APA
Ren, T., Tang, Y., Wang, M., Wang, H., Liu, Y., Qian, X. ... Chen, M. (2020). Triptolide induces apoptosis through the calcium/calmodulin‑dependent protein kinase kinaseβ/AMP‑activated protein kinase signaling pathway in non‑small cell lung cancer cells. Oncology Reports, 44, 2288-2296. https://doi.org/10.3892/or.2020.7763
MLA
Ren, T., Tang, Y., Wang, M., Wang, H., Liu, Y., Qian, X., Chang, C., Chen, M."Triptolide induces apoptosis through the calcium/calmodulin‑dependent protein kinase kinaseβ/AMP‑activated protein kinase signaling pathway in non‑small cell lung cancer cells". Oncology Reports 44.5 (2020): 2288-2296.
Chicago
Ren, T., Tang, Y., Wang, M., Wang, H., Liu, Y., Qian, X., Chang, C., Chen, M."Triptolide induces apoptosis through the calcium/calmodulin‑dependent protein kinase kinaseβ/AMP‑activated protein kinase signaling pathway in non‑small cell lung cancer cells". Oncology Reports 44, no. 5 (2020): 2288-2296. https://doi.org/10.3892/or.2020.7763