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Effect of Punicalagin on Autophagy and Apoptosis in Acute Myeloid Leukemia Cells by Regulating the PI3K/Akt/mTOR Signaling Pathway |
CHANG Feng, ZHANG Linlin |
Zhangjiakou First Hospital, Hebei Zhangjiakou 075000, China |
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Abstract Objective: To investigate the effect of punicalagin (PUN) on autophagy and apoptosis in acute myeloid leukemia (AML) cells by regulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway.Methods: Human AML cells (HL-60) were cultured in vitro and randomly separated into control group (normal culture), L-PUN, M-PUN, H-PUN groups (20, 40, 60 μg/mL PUN), and 740 Y-P group (60 μg/mL PUN+30 μmol/L PI3K/Akt/mTOR signaling pathway activator 740 Y-P). Methylthiazolyltetrazolium (MTT) method and plate cloning method were applied to detect cell proliferation in each group. MDC staining was applied to detect the occurrence of autophagy of cells in various groups. Flow cytometry was applied to detect cell apoptosis in each group. Protein immunoblotting (WB) was applied to detect the expression of apoptosis related proteins (Bcl-2, Bax), autophagy related proteins (P62, LC3-II/I ratio, BECN1), and PI3K/Akt/mTOR signaling pathway related proteins (p-PI3K, p-Akt, p-mTOR) of cells in each group.Results: Compared with the control group, the survival rate, clone count, p-PI3K, p-Akt, p-mTOR, P62, and Bcl-2 protein expression of HL-60 cells in the L-PUN group, M-PUN group, and H-PUN group decreased, while the apoptosis rate, autophagosome positive rate, LC3-II/I ratio, BECN1, and Bax protein expression increased (P<0.05). Compared with the H-PUN group, the survival rate, clone number, p-PI3K, p-Akt, p-mTOR, P62, and Bcl-2 protein expression of the 740 Y-P group cells increased, while the apoptosis rate, autophagosome positive rate, LC3-II/I ratio, BECN1, and Bax protein expression levels decreased (P<0.05).Conclusion: PUN inhibits the PI3K/Akt/mTOR signaling pathway, inhibits HL-60 cell proliferation, promotes apoptosis and autophagy, and slows down the progression of AML.
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[1] Pelcovits A,Niroula R.Acute myeloid leukemia:a review[J].R I Med,2020,103(3):38-40. [2] Kreidieh F,Abou D,Moukalled N,et al.Relapse after allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia:an overview of prevention and treatment[J].Int Hematol,2022,116(3):330-340. [3] Berdowska I,Matusiewicz M,Fecka I.Punicalagin in cancer prevention-via signaling pathways targeting[J].Nutrients,2021,13(8):2733. [4] Subkorn P,Norkaew C,Deesrisak K,et al.Punicalagin,a pomegranate compound,induces apoptosis and autophagy in acute leukemia[J].Peer,2021(9):12303. [5] Shorning BY,Dass MS,Smalley MJ,et al.The PI3K-AKT-mTOR pathway and prostate cancer:at the crossroads of AR,MAPK,and WNT signaling[J].Int Mol Sci,2020,21(12):4507. [6] Sansacar M,Sagil H,Gencer EB.Inhibition of PI3K-AKT-mTOR pathway and modulation of histone deacetylase enzymes reduce the growth of acute myeloid leukemia cells[J].Med Oncol,2023,41(1):31. [7] Rawashde FA,Wajeeh AS,Vishkaei MN,et al.Thymoquinone inhibits JAK/STAT and PI3K/Akt/ mTOR signaling pathways in MV4-11 and K562 myeloid leukemia cells[J].Pharmaceuticals,2022,15(9):1123. [8] Shimony S,Stahl M,Stone RM.Acute myeloid leukemia:2023 update on diagnosis,risk-stratification,and management[J].Am Hematol,2023,98(3):502-526. [9] Vago L,Gojo I.Immune escape and immunotherapy of acute myeloid leukemia[J].Clin Invest,2020,130(4):1552-1564. [10] Sekeres MA,Taylor J.Diagnosis and treatment of myelodysplastic syndromes:a review[J].JAMA,2022,328(9):872-880. [11] Ei-hadary AE,Ramadan MF.Phenolic profiles,antihyperglycemic,antihyperlipidemic,and antioxidant properties of pomegranate (Punica granatum) peel extract[J].Food Biochem,2019,43(4):12803. [12] Ganesan T,Sinniah A,Chik Z,et al.Punicalagin regulates apoptosis-autophagy switch via modulation of annexin A1 in colorectal cancer[J].Nutrients,2020,12(8):2430. [13] Huang L,Lu S,Bian M,et al.Punicalagin attenuates TNF-α-induced oxidative damage and promotes osteogenic differentiation of bone mesenchymal stem cells by activating the Nrf2/HO-1 pathway[J].Exp Cell Res,2023,430(1):113717. [14] De santis MC,Gulluni F,Campa CC,et al.Targeting PI3K signaling in cancer:challenges and advances[J].Biochim Biophys Acta Rev Cancer,2019,1871(2):361-366. [15] Ghareghomi S,Atabaki V,Abdollahzadeh N,et al.Bioactive PI3-kinase/Akt/mTOR inhibitors in targeted lung cancer therapy[J].Adv Pharm Bull,2023,13(1):24-35. [16] Su Y,Wu M,Zhou B,et al.Paclitaxel mediates the PI3K/AKT/mTOR pathway to reduce proliferation of FLT3ITD+AML cells and promote apoptosis[J].Exp Ther Med,2024,27(4):161. |
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