Molecular mechanism of inhibitory effects of melatonin on prostate cancer cell proliferation, migration and invasion.

Altannavch Nyamsambuu,Han-Chun Chen,Xi Zhou,Md Asaduzzaman Khan,Antimo Migliaccio

doi:10.1371/journal.pone.0261341

Altannavch Nyamsambuu, Han-Chun Chen + Show 3 more

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https://doi.org/10.1371/journal.pone.0261341

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Journal: PloS one	Publication Date: Jan 21, 2022
Citations: 8	License type: CC BY 4.0

Affiliation: Central South University, Southwest Medical University

Abstract

The increasing incidence of prostate cancer (PCa) indicates an urgent need for the development of new effective drug therapy. There are limited options to treat the PCa, this study tried to determine a new therapy option for this acute cancer. Androgen-independent PCa cell lines PC3 and DU145 were treated with different melatonin concentrations (0.1~3.5 mM) for 1~3 days and assessed cell migration, cell invasion, cycle arrest in G0/G1 phase as well as apoptosis. We utilized RNA-seq technology to analyze the transcriptional misregulation pathways in DU145 prostate cancer cell line with melatonin (0.5 mM) treatment. Data revealed 20031 genes were up and down-regulated, there were 271 genes that differentially expressed: 97 up-regulated (P<0.05) and 174 down-regulated (P<0.05) genes. Furthermore, RNA-seq results manifested that the melatonin treatment led to a significant increase in the expression levels of HPGD, IL2Rβ, NGFR, however, IGFBP3 and IL6 (P <0.05) had decreased expression levels. The immunoblot assay revealed the expression of IL2Rβ and NGFR genes was up-regulated, qPCR confirmed the gene expression of HPGD and IL2RB were also up-regulated in Du145 cells. Consequently, we probed mechanisms that generate kinetic patterns of NF-κB-dependent gene expression in PCa cells responding to a NF-κB-activation, the significant results were indicated by the inhibition of the NF-kB pathway via IL2Rβ actions. Based on our investigation, it could be concluded that melatonin is a chemotherapeutic molecule against PCa and provides a new idea for clinical therapy of PCa.

Highlights

The hallmarks of cancer assist to understand the cancer, one of the hallmarks of cancer is to avoid the cell mortality [1, 2]
The present study examined two Prostate cancer (PCa) cell lines DU145 and PC3 treated with a range of melatonin concentrations (0.1–3.5mM) for 24, 48, and 72h
Both cell lines revealed sensitivity to melatonin in millimolar range in the dose and timedependent manner investigated by cell proliferation assay, the IC50 value for DU145 is 1.1mM, and for PC3 = 1.0mM treated for 48h (Fig 1A and 1B)

Summary

Introduction

The hallmarks of cancer assist to understand the cancer, one of the hallmarks of cancer is to avoid the cell mortality [1, 2]. The developed countries indicate it as one of the major public health problems among their elderly people so, there is a high demand for new clinical therapies. The incidence of PCa is directly proportional to the demographic changes of population [3, 4]. Prostate cancer (PCa) attains the fourth position being as common cancer, second in male population and contributes 3.8% to deaths due to cancer malignancy [5, 6].

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