title: HDAC1 inhibition by melatonin leads to suppression of lung adenocarcinoma cells via induction of oxidative stress and activation of apoptotic pathways.
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.
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Chongxi
authors.initials: C
authors.lastname: Fan
authors.affiliation: Department of Respiratory Medicine, The 92nd Hospital of PLA, Nanping, China.
authors.forename: Yunhu
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shouyin
authors.initials: S
authors.lastname: Di
authors.affiliation: Department of Aerospace Medicine, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Biomedical Engineering, The Fourth Military Medical University, Xi'an, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Zhipei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Weimiao
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cellular and Structural Biology, UT Health Science Center, San Antonio, TX, USA.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.affiliation: Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Yan
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism*; D000077192:Adenocarcinoma of Lung; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D056284:Histone Deacetylase 1; D005978:Glutathione; D008550:Melatonin
keywords: histone deacetylase inhibitor; histone deacetylases; human lung adenocarcinoma; melatonin