HDAC1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways

Chongxi Fan, Yunhu Pan, Yang Yang, Shouyin Di, Shuai Jiang, Zhiqiang Ma, Tian Li, Zhipei Zhang, Weimiao Li, Xiaofei Li, Russel J Reiter, Xiaolong Yan

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Melatonin is an indoleamine synthesized in the pineal gland that shows a wide range of physiological and pharmacological functions, including anticancer effects. In this study, we investigated the effect of melatonin on drug-induced cellular apoptosis against the cultured human lung adenocarcinoma cells and explored the role of histone deacetylase (HDAC) signaling in this process. The results showed that melatonin treatment led to a dose- and time-dependent decrease in the viability of human A549 and PC9 lung adenocarcinoma cells. Additionally, melatonin exhibited potent anticancer activity in vitro, as evidenced by reductions of the cell adhesion, migration, and the intracellular glutathione (GSH) level and increases in the apoptotic index, caspase 3 activity, and reactive oxygen species (ROS) in A549 and PC9 cells. Melatonin treatment also influenced the expression of HDAC-related molecules (HDAC1 and Ac-histone H3), upregulated the apoptosis-related molecules (PUMA and Bax), and downregulated the proliferation-related molecule (PCNA) and the anti-apoptosis-related molecule (Bcl2). Furthermore, the inhibition of HDAC signaling using HDAC1 siRNA or SAHA (a potent pan-inhibitor of HDACs) sensitized A549 and PC9 cells to the melatonin treatment. In summary, these data indicate that in vitro-administered melatonin is a potential suppressor of lung adenocarcinoma cells by the targeting of HDAC signaling and suggest that melatonin in combination with HDAC inhibitors may be a novel therapeutic intervention for human lung adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)321-333
Number of pages13
JournalJournal of Pineal Research
Volume59
Issue number3
DOIs
StatePublished - Oct 1 2015

Keywords

  • histone deacetylase inhibitor
  • histone deacetylases
  • human lung adenocarcinoma
  • melatonin

ASJC Scopus subject areas

  • Endocrinology

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