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Apigenin, a natural flavonoid has been reported against a variety of cancer types. However, it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells. There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells. We found that iron accumulation, lipid peroxidation, glutathione consumption, p62, HMOX1, and ferritin were increased, while, solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased. Ferrostatin-1, an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells. On the other hand, apigenin could promote autophagy via up-regulating Beclin 1, ULK1, ATG5, ATG13, and LC3B and down-regulating AMPK, mTOR, P70S6K, and ATG4. Furthermore, apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.


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Apigenin, a natural fl avonoid, promotes autophagy and ferroptosis in human endometrial carcinoma Ishikawa cells in vitro and in vivo

Show Author's information Yancui LiangaQian Zhonga,bRunhui Maa,bZhijing Nia,bKiran Thakura,bJianguo Zhanga,bZhaojun Weia,b( )
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
School of Biological Science and Engineering, Collaborative Innovation Center for Food Production and Safety, North Minzu University, Yinchuan 750021, China

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

Apigenin, a natural flavonoid has been reported against a variety of cancer types. However, it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells. There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells. We found that iron accumulation, lipid peroxidation, glutathione consumption, p62, HMOX1, and ferritin were increased, while, solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased. Ferrostatin-1, an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells. On the other hand, apigenin could promote autophagy via up-regulating Beclin 1, ULK1, ATG5, ATG13, and LC3B and down-regulating AMPK, mTOR, P70S6K, and ATG4. Furthermore, apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.

Keywords: Flavonoid, Ferroptosis, Autophagy, Apigenin, Ishikawa cells, Tumor growth, Endometrial carcinoma

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Publication history

Received: 06 June 2022
Revised: 25 July 2022
Accepted: 14 August 2022
Published: 04 April 2023
Issue date: November 2023

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© 2023 Beijing Academy of Food Sciences.

Acknowledgements

Acknowledgements

The authors would like to thank the National Key Research & Development Program of China (2022YFF1100305), the National Natural Science Foundation of Ningxia Province (2021AAC02019), the Major Projects of Science and Technology in Anhui Province (201903a06020021, 201904a06020008, 202004a06020042, 202004a06020052).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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