Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP

Abstract Cancer cells reprogram their energy metabolism pathways, but the mechanisms that enable them to meet their energy demands remain poorly understood. This study investigates the anticancer effects of ethyl p-methoxycinnamate (EMC) in Ehrlich ascites tumor cells (EATCs) and reveals that de nov...

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Main Authors: Yutaro Sasaki, Niina Mizushima, Toshio Norikura, Isao Matsui-Yuasa, Akiko Kojima-Yuasa
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-00131-1
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author Yutaro Sasaki
Niina Mizushima
Toshio Norikura
Isao Matsui-Yuasa
Akiko Kojima-Yuasa
author_facet Yutaro Sasaki
Niina Mizushima
Toshio Norikura
Isao Matsui-Yuasa
Akiko Kojima-Yuasa
author_sort Yutaro Sasaki
collection DOAJ
description Abstract Cancer cells reprogram their energy metabolism pathways, but the mechanisms that enable them to meet their energy demands remain poorly understood. This study investigates the anticancer effects of ethyl p-methoxycinnamate (EMC) in Ehrlich ascites tumor cells (EATCs) and reveals that de novo fatty acid synthesis, rather than glycolysis, plays a pivotal role in sustaining energy homeostasis in cancer cells. EMC significantly reduced ATP levels despite enhancing glycolytic activity. It suppressed the expression of key enzymes involved in de novo fatty acid synthesis, including Acly, Acc1, and Fasn, resulting in decreased intracellular triglyceride (TG) levels. The addition of exogenous palmitic acid reversed EMC-induced ATP depletion and mitigated its anti-proliferative effects. Mechanistically, the ATP reduction caused by EMC was associated with inhibition of the c-Myc/SREBP1 pathway and arrest of the G1/S cell cycle transition. These findings demonstrate that EMC inhibits EATC proliferation by reducing ATP levels via suppression of de novo fatty acid synthesis. This study highlights the critical role of de novo fatty acid synthesis, rather than glycolysis, in maintaining energy homeostasis in cancer cells and provides novel insights into targeting cancer metabolism.
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spelling doaj-art-0d33e4365e564e369ca9bc898d8c2c3a2025-08-20T02:10:50ZengNature PortfolioScientific Reports2045-23222025-05-0115111510.1038/s41598-025-00131-1Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATPYutaro Sasaki0Niina Mizushima1Toshio Norikura2Isao Matsui-Yuasa3Akiko Kojima-Yuasa4Department of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan UniversityDepartment of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan UniversityDepartment of Nutrition, Aomori University of Health and WelfareDepartment of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan UniversityDepartment of Nutrition, Graduate School of Human Life and Ecology, Osaka Metropolitan UniversityAbstract Cancer cells reprogram their energy metabolism pathways, but the mechanisms that enable them to meet their energy demands remain poorly understood. This study investigates the anticancer effects of ethyl p-methoxycinnamate (EMC) in Ehrlich ascites tumor cells (EATCs) and reveals that de novo fatty acid synthesis, rather than glycolysis, plays a pivotal role in sustaining energy homeostasis in cancer cells. EMC significantly reduced ATP levels despite enhancing glycolytic activity. It suppressed the expression of key enzymes involved in de novo fatty acid synthesis, including Acly, Acc1, and Fasn, resulting in decreased intracellular triglyceride (TG) levels. The addition of exogenous palmitic acid reversed EMC-induced ATP depletion and mitigated its anti-proliferative effects. Mechanistically, the ATP reduction caused by EMC was associated with inhibition of the c-Myc/SREBP1 pathway and arrest of the G1/S cell cycle transition. These findings demonstrate that EMC inhibits EATC proliferation by reducing ATP levels via suppression of de novo fatty acid synthesis. This study highlights the critical role of de novo fatty acid synthesis, rather than glycolysis, in maintaining energy homeostasis in cancer cells and provides novel insights into targeting cancer metabolism.https://doi.org/10.1038/s41598-025-00131-1Kaempferia galanga L.Ethyl p-methoxycinnamateDe Novo fatty acid synthesisGlycolysisATPEhrlich Ascites tumor cells
spellingShingle Yutaro Sasaki
Niina Mizushima
Toshio Norikura
Isao Matsui-Yuasa
Akiko Kojima-Yuasa
Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP
Scientific Reports
Kaempferia galanga L.
Ethyl p-methoxycinnamate
De Novo fatty acid synthesis
Glycolysis
ATP
Ehrlich Ascites tumor cells
title Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP
title_full Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP
title_fullStr Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP
title_full_unstemmed Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP
title_short Ethyl p-methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting ATP
title_sort ethyl p methoxycinnamate inhibits tumor growth by suppressing of fatty acid synthesis and depleting atp
topic Kaempferia galanga L.
Ethyl p-methoxycinnamate
De Novo fatty acid synthesis
Glycolysis
ATP
Ehrlich Ascites tumor cells
url https://doi.org/10.1038/s41598-025-00131-1
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