Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress

Liang, Yan-Cui; Zhong, Qian; Ma, Run-Hui; Ni, Zhi‐Jing; Thakur, Kiran; Khan, Mohammad Rizwan; Busquets, Rosa; Zhang, Jianguo; Wei, Zhao‐Jun

doi:10.1016/j.jff.2022.105116

Cited by 14 publications

(8 citation statements)

References 56 publications

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“…Apigenin has been shown to inhibit a variety of human malignancies in vitro and intravenously through a variety of organic actions, including inducing cell death and autophagy, preventing cell cycle progression, and inhibiting cell motility and invasion [35]. In our previous study, we confirmed that apigenin can block Ishikawa cells in the G2/M phase, promote apoptosis and inhibit cell migration and invasion [30]. Here in , we further demonstrated that apigenin can promote cell death through autophagy and ferroptosis.…”

Section: Discussionsupporting

confidence: 62%

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The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

Liang¹,

Zhong²,

Ma³

et al. 2024

Food Science and Human Wellness

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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, GSH consumption, p62, HMOX1, and ferritin were increased, while, SLC7A11 and GPX4 were decreased. Fer-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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Section: Discussionsupporting

confidence: 62%

“…In our previous study, we found that apigenin could inhibit Ishikawa cell activity and promote Ishikawa cell apoptosis with the IC50 of 45.55 μmol/L [30] (Fig. 1 A).…”

Section: Apigenin Induced Ishikawa Cell Death In Vitromentioning

confidence: 79%

The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

Liang¹,

Zhong²,

Ma³

et al. 2024

Food Science and Human Wellness

Self Cite

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“…Numerous studies showed that promotion of apoptosis is responsible for impairing cancer cell viability by flavonoids ( Csapi et al, 2010 ; Souza et al, 2017 ; Lei et al, 2019 ; Raina et al, 2021 ; Zhan and Wei, 2021 ; Liang et al, 2022 ). In our study, santin induced cleavage of caspase-8 and caspase-9, the common features of triggering extrinsic and intrinsic pathways, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment options for cervical cancer include surgery, radiotherapy, and chemotherapy—mainly a combination of cisplatin and paclitaxel, supplemented as needed with anti-VEGF agent bevacizumab ( Cohen et al, 2020 ). To date, inhibition of cell growth or induction of apoptosis by a few flavonoids (e.g., apigenin, chrysin, kaempferol and luteolin) were reported in cervical cancer and endometrial cancer cell lines ( Csapi et al, 2010 ; Lei et al, 2019 ; Raina et al, 2021 ; Zhan and Wei, 2021 ; Liang et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line

Szoka,

Nazaruk,

Giegiel

et al. 2023

Front. Mol. Biosci.

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Cancer of the corpus uteri and cervix uteri, collectively ranks second among new cancer cases in women after breast cancer. Therefore, investigation of new anticancer agents and identifying new molecular targets presents a challenge to improve effectiveness of chemotherapy. In this study, antiproliferative activity of flavonoids derived from the buds of silver birch and downy birch was evaluated in endometrial cancer Ishikawa cells and cervical cancer HeLa cells. It was found that flavanol santin reduced viability of both cell lines better than other flavonoids, including apigenin and luteolin. Moreover, this activity was slightly higher than that induced by the chemotherapy drug, cisplatin. Santin promoted intrinsic and extrinsic apoptosis pathways in cancer cells, but it had low toxicity in normal fibroblasts. The mechanisms of impairing cancer cell viability included induction of oxidative proline catabolism, however in different ways in the cell lines used. In HeLa cells, increase of proline oxidation was due to activation of p53 leading to proline oxidase upregulation. In contrast, in Ishikawa cells, having basal proline oxidase level significantly higher than HeLa cells, santin treatment decreased its expression. Nevertheless, proline oxidation was induced in these cells since santin increased expression and activity of prolidase, an enzyme providing proline from protein degradation. In both cell lines, proline oxidation was associated with generation of reactive oxygen species leading to reduction in cell viability. Our findings reveal the involvement of proline oxidase in induction of apoptosis by santin and identify a role of prolidase in proline oxidase-dependent apoptosis.

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“…After that, 1 mL of trypsin was added for cell digestion. After digestion, the reaction was terminated with 1 mL of fresh medium followed by centrifugation (1200 rpm, 5 min) [ 21 ]. After centrifugation, the supernatant was discarded and 1 mL of fresh medium was added to resuspend the cells.…”

Section: Methodsmentioning

confidence: 99%

Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo

Zhang

et al. 2022

Foods

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Endometrial cancer (EC) is a very common female cancer which has attracted more and more attention. According to the individual patient’s condition, the current treatment of EC patients is mainly based on surgery, which is supplemented by chemotherapy, radiotherapy, and endocrine intervention. However, these existing treatment strategies also have some inevitable limitations. Therefore, it is particularly important to find an active ingredient with low toxicity and a high safety profile against EC. Isorhamnetin is a flavonoid known to be present in a variety of plants, such as sea buckthorn, dry willow, and wolfberry. In recent years, the anti-tumor effects of isorhamnetin have been reported. In our study, isorhamnetin was shown to induce apoptosis in Ishikawa cells by inducing the endogenous mitochondrial apoptotic pathway and exogenous death receptor pathway, promoting the endoplasmic reticulum stress-related pathway, and activating the corresponding markers of UPR response. In addition, isorhamnetin affected the expression of MMP2 and MMP9-related proteins in vitro and in vivo and eventually repressed metastasis. Therefore, isorhamnetin can be used as a promising medicinal material for the treatment of EC.

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Apigenin inhibits migration and induces apoptosis of human endometrial carcinoma Ishikawa cells via PI3K-AKT-GSK-3β pathway and endoplasmic reticulum stress

Cited by 14 publications

References 56 publications

The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

The modulatory effect of oolong tea polyphenols on intestinal flora and hypothalamus gene expression in a circadian rhythm disturbance mouse model

Prolidase-proline oxidase axis is engaged in apoptosis induction by birch buds flavonol santin in endometrial adenocarcinoma cell line

Isorhamnetin Induces Apoptosis and Suppresses Metastasis of Human Endometrial Carcinoma Ishikawa Cells via Endoplasmic Reticulum Stress Promotion and Matrix Metalloproteinase-2/9 Inhibition In Vitro and In Vivo

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