Thymoquinone Augments Cisplatin-Induced Apoptosis on Esophageal Carcinoma Through Mitigating the Activation of JAK2/STAT3 Pathway

Dig Dis Sci. 2018 Jan;63(1):126-134. doi: 10.1007/s10620-017-4856-8. Epub 2017 Dec 2.

Abstract

Background: Thymoquinone (TQ) is the major constituent of Nigella sativa seed and has shown biological activity in various human carcinomas. However, few studies have reported its effect on esophageal carcinoma (EC).

Aims: To explore the chemosensitive effect and mechanism of TQ in augmentation of cisplatin (DDP)-induced apoptosis of EC, both in vitro and in vivo.

Methods: The viability and apoptosis of esophageal carcinoma cells were detected by the Cell Counting Kit-8 assay, flow cytometry, and Hoechst 33258 staining. The expression levels of JAK2, p-JAK2, STAT3, p-STAT3, Bax, Bcl-2, Cyclin D1, Survivin, and caspase-3, 7, 9 were evaluated by western blot analysis. The histological changes were examined by TUNEL technique and immunohistochemical analysis.

Results: TQ enhanced the proapoptotic effect of DDP in human esophageal carcinoma cell line Eca-109, while blocking the activation of JAK2/STAT3 signaling pathway. The apoptosis of esophageal carcinoma cells was induced via blocking the activation of JAK2/STAT3 by using a molecular inhibitor (WP1066). Consistent with the in vivo and in vitro results, TQ increased cellular apoptosis and enriched the chemosensitivity of DDP.

Conclusions: TQ along with DDP may regulate the progression of EC and has potential to be a chemotherapeutic agent in EC.

Keywords: Apoptosis; Esophageal carcinoma; STAT3; Thymoquinone; WP1066.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Benzoquinones / administration & dosage
  • Benzoquinones / pharmacokinetics
  • Benzoquinones / pharmacology*
  • Bisbenzimidazole
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cisplatin / pharmacokinetics
  • Cisplatin / pharmacology*
  • Drug Synergism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Janus Kinase 2 / metabolism*
  • STAT3 Transcription Factor / metabolism*

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • JAK2 protein, human
  • Janus Kinase 2
  • Bisbenzimidazole
  • thymoquinone
  • Cisplatin