Retracted: 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.

Novel Protective Role for Ubiquitin-Specific Protease 18 in Pathological Cardiac Remodeling

“…18 We used SPSS 19.0 software to perform the statistical analysis in this study. Student unpaired t tests (between 2 groups) and 1-way ANOVA (for >2 groups) followed by Bonferroni (equal variances assumed) or Tamhane T2 (equal variances not assumed) were used where applicable.…”

Melatonin as a potential anticarcinogen for non-small-cell lung cancer

“…As a potent free radical scavenger and antioxidant, melatonin has the capacity to scavenge up to 10 reactive oxygen species (ROS) via the cascade reaction means, which distinguishes melatonin from the classic antioxidants that scavenge only one or less ROS [11–13]. Additionally, numerous publications have reported that melatonin inhibits the growth of a variety of cancers: lung [5, 14, 15], breast [16–20], prostate [21–24], liver [25, 26], colon [27, 28], etc. The oncostatic mechanisms of melatonin are related to several hallmarks of cancer, including anti-proliferation [14], induction of apoptosis [5, 14, 15], inhibition of invasion and metastasis [29, 30], anti-angiogenesis [16, 31], and enhancement of immunomodulation [32] among others.…”

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…HDAC1s are frequently overexpressed in various types of human cancer, melatonin treatment decreasing expression of HDAC1 [64]. Fan et al reported that melatonin acts as a suppressor in colorectal cancer cells and osteosarcoma cells via HDAC signaling inhibition.…”

“…Fan et al reported that melatonin acts as a suppressor in colorectal cancer cells and osteosarcoma cells via HDAC signaling inhibition. On the other hand, HDAC1 inhibitors induce ROS production, so oxidative stress might be an important mechanism by which melatonin induces cancer cell death [64].…”