Open Access

Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells

  • Authors:
    • Shao‑Jun Li
    • Shi‑Jie Sun
    • Jie Gao
    • Fu‑Bo Sun
  • View Affiliations

  • Published online on: November 8, 2016     https://doi.org/10.3892/ol.2016.5367
  • Pages: 5059-5067
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti‑cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells. The mechanism of wogonin‑related autophagy was investigated, and the antioxidant N‑acetyl‑L‑cysteine (NAC) was used to assess the role of reactive oxygen species (ROS) in wogonin‑related autophagy. The results demonstrated that wogonin may induce autophagy by activating the Beclin‑1/phosphatidylinositol‑3‑kinase and ROS pathways in HPCCs, and may enhance ROS generation, followed by the activation of the AKT/ULK1/4E‑BP1/CYLD pathway and inhibition of the mammalian target of rapamycin signaling pathway. The incubation of HPCCs with wogonin and the antioxidant NAC, revealed that the effects of wogonin‑enhanced ROS generation on autophagy‑related molecules were inhibited, contributing to the inhibition of autophagy and increasing the cell death ratio through apoptosis activation in HPCCs. These studies suggest that autophagy activation, via the ROS pathway, by the antitumor drug wogonin in HPCCs may partially reduce the antitumor effects of the drug, and that the antioxidant NAC may enhance the antitumor effectiveness of wogonin via the inhibition of ROS‑enhanced autophagy and the subsequent promotion of apoptosis. Therefore, the present research suggests that wogonin combined with NAC may be a novel combination therapy for clinical pancreatic cancer therapy trials.
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December-2016
Volume 12 Issue 6

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Li SJ, Sun SJ, Gao J and Sun FB: Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells. Oncol Lett 12: 5059-5067, 2016
APA
Li, S., Sun, S., Gao, J., & Sun, F. (2016). Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells. Oncology Letters, 12, 5059-5067. https://doi.org/10.3892/ol.2016.5367
MLA
Li, S., Sun, S., Gao, J., Sun, F."Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells". Oncology Letters 12.6 (2016): 5059-5067.
Chicago
Li, S., Sun, S., Gao, J., Sun, F."Wogonin induces Beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells". Oncology Letters 12, no. 6 (2016): 5059-5067. https://doi.org/10.3892/ol.2016.5367