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Apigenin inhibits the proliferation and aerobic glycolysis of endometrial cancer cells by regulating the PI3K/Akt signaling pathway
1Department of Obstetrics and Gynecology, Affiliated Hospital of Beihua University, 132011 Jilin, Jilin, China
2Department of Obstetrics and Gynecology, Basic Medical College of Beihua University, 132013 Jilin, Jilin, China
3Department of Immunology, Medical Technology College of Beihua University, 132013 Jilin, Jilin, China
DOI: 10.22514/ejgo.2024.100 Vol.45,Issue 5,October 2024 pp.125-131
Submitted: 04 June 2024 Accepted: 08 July 2024
Published: 15 October 2024
*Corresponding Author(s): Yongchao Liu E-mail: liuyongchao@126.com
This study investigated the effects of apigenin on endometrial cancer cell proliferation, apoptosis and aerobic glycolysis. The cell viability and cell proliferation of endometrial cancer cells were detected using Cell Counting Kit-8 (CCK8) kit and5-ethynyl-2′-deoxyuridine (EDU) staining. Flow cytometry analysis was used to detect the rate of apoptosis in endometrial cancer cells. Lactate production, glucose consumption, and Adenosine triphosphate (ATP) levels were also measured. Western blot was used to detect the expression of Bcl2-Associated X (BAX), B-cell lymphoma 2 (BCL-2), Cleaved Caspase-3, phosphoinositide 3-kinase (PI3K), p-PI3K, rapamycin (mTOR), p-mTOR, Phosphatase and tensin homolog (PTEN), protein kinase B (Akt) and p-Akt. The results showed that, apigenin inhibits cell viability, cell proliferation, promotes the rate of apoptosis, and the expression of BAX, Cleaved Caspase-3, and inhibits the expression of BCL-2 of endometrial cancer cells in a dose-dependent manner. In addition, apigenin suppressed lactate production, glucose consumption, and ATP levels and inhibited the phosphorylation of PI3K and Akt in a dose-dependent manner. Finally, apigenin inhibited the proliferation and aerobic glycolysis of endometrial cancer cells and promoted cell apoptosis by blocking the PI3K/Akt signaling pathway.
Endometrial cancer; Apigenin; PI3K/Akt; Cell proliferation; Apoptosis; Aerobic glycolysis
Li Xu,Lu Peng,Tingting Cao,Limei Zhang,Mo Li,Yongchao Liu. Apigenin inhibits the proliferation and aerobic glycolysis of endometrial cancer cells by regulating the PI3K/Akt signaling pathway. European Journal of Gynaecological Oncology. 2024. 45(5);125-131.
[1] Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023; 73: 17–48.
[2] King L, Gajarawala S, McCrary MD. Endometrial cancer and obesity: addressing the awkward silence. JAAPA. 2023; 36: 28–31.
[3] Crosbie EJ, Kitson SJ, McAlpine JN, Mukhopadhyay A, Powell ME, Singh N. Endometrial cancer. The Lancet. 2022; 399: 1412–1428.
[4] Wang Y, Wang G, Liu Y, Yang F, Zhang H, Kong Y. Icaritin inhibits endometrial carcinoma cells by suppressing O-GlcNAcylation of FOXC1. Phytomedicine. 2023; 120: 155062.
[5] Guo D, Tong Y, Jiang X, Meng Y, Jiang H, Du L, et al. Aerobic glycolysis promotes tumor immune evasion by hexokinase2-mediated phosphorylation of IκBα. Cell Metabolism. 2022; 34: 1312–1324.e6.
[6] Han X, Ren C, Yang T, Qiao P, Wang L, Jiang A, et al. Negative regulation of AMPKα1 by PIM2 promotes aerobic glycolysis and tumorigenesis in endometrial cancer. Oncogene. 2019; 38: 6537–6549.
[7] Xu L, Zaky MY, Yousuf W, Ullah A, Abdelbaset GR, Zhang Y, et al. The anticancer potential of apigenin via immunoregulation. Current Pharmaceutical Design. 2021; 27: 479–489.
[8] Singh D, Gupta M, Sarwat M, Siddique HR. Apigenin in cancer prevention and therapy: a systematic review and meta-analysis of animal models. Critical Reviews in Oncology/Hematology. 2022; 176: 103751.
[9] Hnit SST, Yao M, Xie C, Bi L, Wong M, Liu T, et al. Apigenin impedes cell cycle progression at G2 phase in prostate cancer cells. Discover Oncology. 2022; 13: 44.
[10] Chen Z, Tian D, Liao X, Zhang Y, Xiao J, Chen W, et al. Apigenin combined with gefitinib blocks autophagy flux and induces apoptotic cell death through inhibition of HIF-1α, c-Myc, p-EGFR, and glucose metabolism in EGFR L858R+T790M-mutated H1975 cells. Frontiers in Pharmacology. 2019; 10: 260.
[11] Jia C, Zhao Y, Huang H, Fan K, Xie T, Xie M. Apigenin sensitizes radiotherapy of mouse subcutaneous glioma through attenuations of cell stemness and DNA damage repair by inhibiting NF-κB/HIF-1α-mediated glycolysis. The Journal of Nutritional Biochemistry. 2022; 107: 109038.
[12] Shi Y, Lian K, Jia J. Apigenin suppresses the Warburg effect and stem-like properties in SOSP-9607 cells by inactivating the PI3K/Akt/mTOR signaling pathway. Evidence-Based Complementary and Alternative Medicine. 2022; 2022: 3983637.
[13] Yang C, Song J, Hwang S, Choi J, Song G, Lim W. Apigenin enhances apoptosis induction by 5-fluorouracil through regulation of thymidylate synthase in colorectal cancer cells. Redox Biology. 2021; 47: 102144.
[14] Ahmed SA, Parama D, Daimari E, Girisa S, Banik K, Harsha C, et al. Rationalizing the therapeutic potential of apigenin against cancer. Life Sciences. 2021; 267: 118814.
[15] Lopez A, Reyna DE, Gitego N, Kopp F, Zhou H, Miranda-Roman MA, et al. Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer. Nature Communications. 2022; 13: 1199.
[16] Dong L, Chen M, Huang Z, Tan Y, Zhang C, Zhang S, et al. A new labdane diterpenoid from Scoparia dulcis improving pancreatic function against islets cell apoptotic by Bax/Bcl-2/Caspase-3 pathway. Journal of Ethnopharmacology. 2024; 322: 117571.
[17] Apicella M, Giannoni E, Fiore S, Ferrari KJ, Fernández-Pérez D, Isella C, et al. Increased lactate secretion by cancer cells sustains non-cell-autonomous adaptive resistance to MET and EGFR targeted therapies. Cell Metabolism. 2018; 28: 848–865.e6.
[18] de la Cruz-López KG, Castro-Muñoz LJ, Reyes-Hernández DO, García-Carrancá A, Manzo-Merino J. Lactate in the regulation of tumor microenvironment and therapeutic approaches. Frontiers in Oncology. 2019; 9: 1143.
[19] Pérez-Tomás R, Pérez-Guillén I. Lactate in the tumor microenvironment: an essential molecule in cancer progression and treatment. Cancers; 2020; 12: 3244.
[20] Ruan GX, Kazlauskas A. Lactate engages receptor tyrosine kinases Axl, Tie2, and vascular endothelial growth factor receptor 2 to activate phosphoinositide 3-kinase/Akt and promote angiogenesis. The Journal of Biological Chemistry. 2013; 288: 21161–21172.
[21] Wu Z, Wu J, Zhao Q, Fu S, Jin J. Emerging roles of aerobic glycolysis in breast cancer. Clinical & Translational Oncology. 2020; 22: 631–646.
[22] Zhuo B, Li Y, Li Z, Qin H, Sun Q, Zhang F, et al. PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma. Biochemical and Biophysical Research Communications. 2015; 464: 401–406.
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