褪黑激素改变卵巢癌细胞的能量代谢并减少致癌信号传导

IF 3.8 3区 医学 Q2 CELL BIOLOGY Molecular and Cellular Endocrinology Pub Date : 2024-06-04 DOI:10.1016/j.mce.2024.112296
Henrique Spaulonci Silveira , Roberta Carvalho Cesário , Renan Aparecido Vígaro , Leticia Barbosa Gaiotte , Maira Smaniotto Cucielo , Fernando Guimarães , Fábio Rodrigues Ferreira Seiva , Debora Aparecida P.C. Zuccari , Russel J. Reiter , Luiz Gustavo de Almeida Chuffa
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引用次数: 0

摘要

卵巢癌(OC)会调整能量代谢以促进其发展和扩散。由于褪黑激素(Mel)具有抗肿瘤作用,我们研究了它对卵巢癌细胞(SKOV-3 和 CAISMOV-24)能量代谢和激酶信号转导的影响。细胞被分为对照组和 Mel 处理组,在有或没有拮抗剂吕吲哚的情况下。即使在有吕吲哚存在的情况下,两种 OC 细胞中的 HIF-1α、G6PDH、GAPDH、PDH 和 CS 水平在经 Mel 处理后都有所下降。梅尔处理还降低了与 OC 相关的酶的活性,包括 PFK-1、G6PDH、LDH、CS 和 GS,而 PDH 的活性则有所增加。经 Mel 处理后,乳酸和谷氨酰胺水平下降。Mel 进一步促进了两种细胞系中 CREB、JNK、NF-kB、p-38、ERK1/2、AKT、P70S6K 和 STAT 浓度的降低。Mel能逆转沃伯格型新陈代谢,并可能减少谷氨酰胺溶解,从而抑制与OC进展和侵袭相关的各种致癌分子。
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Melatonin changes energy metabolism and reduces oncogenic signaling in ovarian cancer cells

Ovarian cancer (OC) adjusts energy metabolism in favor of its progression and dissemination. Because melatonin (Mel) has antitumor actions, we investigated its impact on energy metabolism and kinase signaling in OC cells (SKOV-3 and CAISMOV-24). Cells were divided into control and Mel-treated groups, in the presence or absence of the antagonist luzindole. There was a decrease in the levels of HIF-1α, G6PDH, GAPDH, PDH, and CS after Mel treatment even in the presence of luzindole in both OC cells. Mel treatment also reduced the activity of OC-related enzymes including PFK-1, G6PDH, LDH, CS, and GS whereas PDH activity was increased. Lactate and glutamine levels dropped after Mel treatment. Mel further promoted a reduction in the concentrations of CREB, JNK, NF-kB, p-38, ERK1/2, AKT, P70S6K, and STAT in both cell lines. Mel reverses Warburg-type metabolism and possibly reduces glutaminolysis, thereby attenuating various oncogenic molecules associated with OC progression and invasion.

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来源期刊
Molecular and Cellular Endocrinology
Molecular and Cellular Endocrinology 医学-内分泌学与代谢
CiteScore
9.00
自引率
2.40%
发文量
174
审稿时长
42 days
期刊介绍: Molecular and Cellular Endocrinology was established in 1974 to meet the demand for integrated publication on all aspects related to the genetic and biochemical effects, synthesis and secretions of extracellular signals (hormones, neurotransmitters, etc.) and to the understanding of cellular regulatory mechanisms involved in hormonal control.
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