Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis

  • Authors:
    • Bee-Jen Tan
    • Gigi N.C. Chiu
  • View Affiliations

  • Published online on: March 1, 2013     https://doi.org/10.3892/ijo.2013.1843
  • Pages: 1605-1612
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Abstract

Since its isolation from Tripterygium wilfordii in 1972, triptolide has been shown to possess potent anticancer activity against a variety of cancers, and has entered phase I clinical trial. It is a diterpenoid triepoxide that acts through multiple molecular targets and signaling pathways. The mitogen-activated protein kinases are well known for their modulation of cell survival and proliferation. In particular, the ERK pathway has a dual role in cell proliferation and cell death. Thus far, data on the effect of triptolide on ERK signaling remain limited. In our current study, we have shown for the first time that ERK activation rather than inhibition occurred in a dose- and time-dependent manner following triptolide treatment in MDA-MB-231 breast cancer cells. ERK activation was crucial in mediating triptolide-induced caspase-dependent apoptosis. Tritpolide-induced ERK activation modulated the expression of the Bcl-2 protein family member Bax but was not involved in the downregulation of Bcl-xL expression. Signals acted upstream of ERK activation included generation of reactive oxygen species (ROS) and endoplasmic reticulum stress predominantly via the PERK‑eIF2α pathway, as the MEK inhibitor U0126 did not inhibit the phosphorylation of PERK and eIF2α or the generation of ROS.
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May 2013
Volume 42 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Tan B and Tan B: Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis. Int J Oncol 42: 1605-1612, 2013
APA
Tan, B., & Tan, B. (2013). Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis. International Journal of Oncology, 42, 1605-1612. https://doi.org/10.3892/ijo.2013.1843
MLA
Tan, B., Chiu, G. N."Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis". International Journal of Oncology 42.5 (2013): 1605-1612.
Chicago
Tan, B., Chiu, G. N."Role of oxidative stress, endoplasmic reticulum stress and ERK activation in triptolide-induced apoptosis". International Journal of Oncology 42, no. 5 (2013): 1605-1612. https://doi.org/10.3892/ijo.2013.1843