Abstract

The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.

Original languageEnglish
Article numbere12620
JournalJournal of Pineal Research
Volume68
Issue number1
DOIs
Publication statusPublished - Jan 1 2020

Fingerprint

Leiomyoma
Melatonin
Cell Death
Cell Proliferation
Myometrium
Growth
Smooth Muscle Myocytes
Melatonin MT1 Receptor
Melatonin MT2 Receptor
PTEN Phosphohydrolase
Apoptosis
Breast Neoplasms
Neoplasms
Autophagy
G1 Phase
Heterografts
Ovarian Neoplasms
Extracellular Matrix
Cell Cycle
Up-Regulation

Keywords

  • apoptosis
  • autophagy
  • cell cycle
  • melatonin
  • uterine leiomyoma (fibroid)
  • uterine smooth muscle cells

ASJC Scopus subject areas

  • Endocrinology

Cite this

Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation. / Lin, Po Han; Tung, Yen Ting; Chen, Hsin Yuan; Chiang, Yi Fen; Hong, Hui Chih; Huang, Ko Chieh; Hsu, Sung Po; Huang, Tsui Chin; Hsia, Shih Min.

In: Journal of Pineal Research, Vol. 68, No. 1, e12620, 01.01.2020.

Research output: Contribution to journalArticle

Lin, Po Han ; Tung, Yen Ting ; Chen, Hsin Yuan ; Chiang, Yi Fen ; Hong, Hui Chih ; Huang, Ko Chieh ; Hsu, Sung Po ; Huang, Tsui Chin ; Hsia, Shih Min. / Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation. In: Journal of Pineal Research. 2020 ; Vol. 68, No. 1.
@article{f3ab726aa5d24508a36781bd5bdd69fd,
title = "Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation",
abstract = "The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.",
keywords = "apoptosis, autophagy, cell cycle, melatonin, uterine leiomyoma (fibroid), uterine smooth muscle cells",
author = "Lin, {Po Han} and Tung, {Yen Ting} and Chen, {Hsin Yuan} and Chiang, {Yi Fen} and Hong, {Hui Chih} and Huang, {Ko Chieh} and Hsu, {Sung Po} and Huang, {Tsui Chin} and Hsia, {Shih Min}",
year = "2020",
month = "1",
day = "1",
doi = "10.1111/jpi.12620",
language = "English",
volume = "68",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Melatonin activates cell death programs for the suppression of uterine leiomyoma cell proliferation

AU - Lin, Po Han

AU - Tung, Yen Ting

AU - Chen, Hsin Yuan

AU - Chiang, Yi Fen

AU - Hong, Hui Chih

AU - Huang, Ko Chieh

AU - Hsu, Sung Po

AU - Huang, Tsui Chin

AU - Hsia, Shih Min

PY - 2020/1/1

Y1 - 2020/1/1

N2 - The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.

AB - The circadian nature of melatonin has a protective effect on the progression of female reproductive cancers, including breast and ovarian cancers. However, the effect of melatonin on the growth of uterine leiomyoma is still unclear. In this study, we found that the growth of uterine leiomyoma ELT3 cells was reduced by treatment with melatonin. Treatment with melatonin increased the distribution of sub-G1 phase and increased DNA condensation in ELT3 cells. Melatonin-induced apoptosis and autophagy cell death progression were observed in ELT3 cells. Melatonin exerts a highly selective effect on primary normal human uterine smooth muscle (UtSMC) cells. The UtSMC cell cycle was arrested by melatonin treatment through up-regulation of p21, p27, and PTEN protein expression, but melatonin did not further promote apoptosis program activation. Melatonin reduced cell proliferation in ELT3 cells underlying the activation of melatonin MT1 and MT2 receptors, which in turn down-regulated the Akt-ERK1/2-NFκB signaling pathway. Melatonin reduced ELT3 tumor growth in both xenograft and orthotopic uterine tumor mice models. The extracellular matrix of the tumor was also reduced by melatonin treatment. Taken together, these results suggest that melatonin potentially plays a role in suppression of uterine leiomyoma growth.

KW - apoptosis

KW - autophagy

KW - cell cycle

KW - melatonin

KW - uterine leiomyoma (fibroid)

KW - uterine smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=85075751064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075751064&partnerID=8YFLogxK

U2 - 10.1111/jpi.12620

DO - 10.1111/jpi.12620

M3 - Article

C2 - 31710386

AN - SCOPUS:85075751064

VL - 68

JO - Journal of Pineal Research

JF - Journal of Pineal Research

SN - 0742-3098

IS - 1

M1 - e12620

ER -