Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase‑1 expression in cholangiocarcinoma cell lines

  • Authors:
    • Chutima Talabnin
    • Krajang Talabnin
    • Sopit Wongkham
  • View Affiliations

  • Published online on: June 26, 2020     https://doi.org/10.3892/ol.2020.11784
  • Pages: 2483-2492
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Piperlongumine (PL) produces reactive oxygen species (ROS) and induces G2/M‑phase arrest in cholangiocarcinoma (CCA) cells via the JNK/ERK pathway. A differential response to PL was observed among all CCA cell lines However, the underlying mechanisms have remained to be fully elucidated. The aim of the present study was to investigate the molecular mechanisms of PL‑induced heme oxygenase‑1 (HO‑1) expression in CCA cell lines. The anti‑proliferative action of PL in the CCA cell lines KKU‑100 and KKU‑213A was analyzed using sulforhodamine B assays. Reverse transcription‑quantitative PCR and western blot analyses were used to examine mRNA and protein expression. HO‑1 inhibition was achieved using the chemical inhibitor zinc protophoryn or specific small interfering RNA to HO‑1. Intracellular ROS was detected using a 2',7'‑dichlorodihydrofluorescein diacetate fluorescence assay. High expression of phase‑II detoxification enzymes, including NADPH quinone oxidoreductase‑1, heme oxygenase‑1, superoxide dismutases and aldo‑keto reductase 1 subunits C‑1 and 3, were detected in the KKU‑100 cell line. Of the CCA cell lines tested, KKU‑100 was the least sensitive to PL. Dose‑dependent upregulation of HO‑1 expression via PI3K/Akt activation was detected in PL‑treated CCA cells. Inhibition of HO‑1 eliminated the antioxidant defense mechanisms, leading to increased anti‑cancer activity of PL in the CCA cell lines via an increase in intracellular ROS levels and apoptotic protein expression. These observations indicated that HO‑1 inhibition had a chemosensitizing effect on CCA to PL.

Related Articles

Journal Cover

September-2020
Volume 20 Issue 3

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Talabnin C, Talabnin K and Wongkham S: Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase‑1 expression in cholangiocarcinoma cell lines. Oncol Lett 20: 2483-2492, 2020
APA
Talabnin, C., Talabnin, K., & Wongkham, S. (2020). Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase‑1 expression in cholangiocarcinoma cell lines. Oncology Letters, 20, 2483-2492. https://doi.org/10.3892/ol.2020.11784
MLA
Talabnin, C., Talabnin, K., Wongkham, S."Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase‑1 expression in cholangiocarcinoma cell lines". Oncology Letters 20.3 (2020): 2483-2492.
Chicago
Talabnin, C., Talabnin, K., Wongkham, S."Enhancement of piperlongumine chemosensitivity by silencing heme oxygenase‑1 expression in cholangiocarcinoma cell lines". Oncology Letters 20, no. 3 (2020): 2483-2492. https://doi.org/10.3892/ol.2020.11784