Melatonin inhibits colon cancer RKO cell migration by downregulating Rho‑associated protein kinase expression via the p38/MAPK signaling pathway

Print
Published on Wednesday, 22 November 2017

Abstract

Melatonin is predominately produced and secreted by the pineal gland, and inhibits cell growth in various cancer cell lines such as colorectal cancer. However, the precise mechanisms involved have not been fully elucidated.

In the present study, the potential molecular mechanism underlying the efficacy of melatonin on migration in RKO colon cancer cells was investigated.

The effects of melatonin and H‑1152, a selective inhibitor of Rho‑associated protein kinase (ROCK), on the migration of RKO cells were analyzed by an in vitro wound healing assay. The localization of zonula occludens‑1 (ZO‑1) and occludin were observed by immunofluorescence. Reverse transcription‑quantitative polymerase chain reaction (qPCR) was performed to analyze the relative mRNA levels of ROCK, ZO‑1 and occludin.

In addition, western blot analysis was implemented to examine the expression of ROCK, phospho (p)‑myosin phosphatase targeting subunit 1 (MYPT1), p‑myosin light chains (MLC) and p‑p38.

The results revealed that the expression levels of ROCK2, p‑MYPT1 and p‑MLC in RKO cells were decreased, and the membrane protein expression of ZO‑1 and occludin increased when the cells were treated with melatonin. qPCR demonstrated that melatonin downregulated ROCK2 gene expression, and upregulated the expression of the ZO‑1 and occludin genes. The levels of ZO‑1 and occludin localized in the tight junctions were markedly increased in the immunofluorescence assay.

In addition, the phosphorylation levels of p38 were reduced when the cells were treated with melatonin, and treatment with H‑1152 downregulated p38 phosphorylation.

The results indicated that melatonin may inhibit the migration of RKO colon cancer cells by downregulating ROCK expression via the p38/mitogen‑activated protein kinase signaling pathway.

 

 

About this publication.

 

See also:

- About Melatonin;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonisn, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.