Open Access

Neferine treatment enhances the TRAIL‑induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway

  • Authors:
    • Uddin MD Nazim
    • Honghua Yin
    • Sang‑Youel Park
  • View Affiliations

  • Published online on: March 13, 2020     https://doi.org/10.3892/ijo.2020.5012
  • Pages: 1152-1161
  • Copyright: © Nazim et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PCa) is a common type of cancer among males, with a relatively high mortality rate. Tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, initiates the apoptosis of certain cancer cells. Neferine, a primary ingredient of bisbenzylisoquinoline alkaloids, has various antitumor activities. The present study examined the effects of neferine treatment on human PCa cells. Human prostate cancer (DU145) cells were treated with neferine for 18 h, and subsequently treated with TRAIL for 2 h. Combined treatment with neferine and TRAIL significantly decreased cell viability compared to treatment with TRAIL alone. Furthermore, neferine treatment decreased the expression of p62 and increased LC3B‑II expression, as assessed by western blot analysis and immunocytochemistry. It was alsp demonstrated that neferine and TRAIL act synergistically to trigger autophagy in PCa cells, as revealed by autophagosome formation, LC3B‑II accumulation demonstrated by transmission electron microscopy (TEM) analysis and phosphorylated c‑Jun N‑terminal kinase (p‑JNK) upregulation. When the autophagic flux was attenuated by the inhibitor, chloroquine, or by genetically modified ATG5 siRNA, the enhancement of TRAIL‑induced autophagy by neferine‑induced was also attenuated. Furthermore, treatment with the JNK inhibitor, SP600125, distinctly increased the viability of the cells treated with neferine and TRAIL. On the whole, the findings of the present study demonstrate that neferine treatment effectively promotes TRAIL‑mediated cell death and this effect likely occurs via the autophagic flux and the JNK pathway.

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May 2020
Volume 56 Issue 5

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

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APA
Nazim, U.M., Yin, H., & Park, S. (2020). Neferine treatment enhances the TRAIL‑induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway. International Journal of Oncology, 56, 1152-1161. https://doi.org/10.3892/ijo.2020.5012
MLA
Nazim, U. M., Yin, H., Park, S."Neferine treatment enhances the TRAIL‑induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway". International Journal of Oncology 56.5 (2020): 1152-1161.
Chicago
Nazim, U. M., Yin, H., Park, S."Neferine treatment enhances the TRAIL‑induced apoptosis of human prostate cancer cells via autophagic flux and the JNK pathway". International Journal of Oncology 56, no. 5 (2020): 1152-1161. https://doi.org/10.3892/ijo.2020.5012