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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Baicalein Promotes Acute Myeloid Leukemia Cell Autophagy via miR-424 and the PTEN/PI3K/AKT/mTOR Pathway

Author(s): Qi Li and Jinhai Ren*

Volume 21, Issue 6, 2024

Published on: 14 March, 2023

Page: [1095 - 1102] Pages: 8

DOI: 10.2174/1570180820666230217092156

Price: $65

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Abstract

Objective: To explore the autophagic effect of baicalein on acute myeloid leukemia (AML) cell lines, HL-60 and THP-1, and miR-424, which regulates the baicalein effect on HL-60 and THP-1 in which autophagy was observed.

Methods: The cell counting kit-8 (CCK-8) assay was used to detect the optimal concentration of baicalein in the HL-60 and THP-1 cell lines. miR-424 was detected by qPCR. The influence of baicalein on the autophagy of the HL-60 and THP-1 cells was demonstrated by detecting the expression of Beclin-1, LC3- I, and LC3-II using western blot. The phosphatase and tensin homolog (PTEN)/PI3K/AKt/mTOR pathways were determined by western blot.

Results: The optimum concentration of baicalein used and the time of treatment in the HL-60 and THP-1 cell lines were 40 μM and 48 hours, respectively. The expression of miR-424 in the baicalein-treated cells was lower than that in the blank group both in the HL-60 cells and THP-1 cells. The expression of PTEN was promoted by baicalein. However, baicalein inhibited PI3K expression, mTOR phosphorylation, and AKT phosphorylation in the two cell lines. LC3-Ⅰ/Ⅱ, which is the biomarker for autophagy, increased after the cells were treated with baicalein. The baseline expression also increased after the cells were treated with baicalein.

Conclusion: Baicalein could promote the autophagy of the HL-60 and THP-1 cells via miR-424 and the PTEN/ PI3K/AKT/mTOR pathway.

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[1]
Jimbu, L.; Mesaros, O.; Neaga, A.; Nanut, A.M.; Tomuleasa, C.; Dima, D.; Bocsan, C.; Zdrenghea, M. The potential advantage of targeting both PD-L1/PD-L2/PD-1 and IL-10–IL-10R pathways in acute myeloid leukemia. Pharmaceuticals, 2021, 14(11), 1105.
[http://dx.doi.org/10.3390/ph14111105] [PMID: 34832887]
[2]
Khaldoyanidi, S.K.; Hindoyan, A.; Stein, A.; Subklewe, M. Leukemic stem cells as a target for eliminating acute myeloid leukemia: Gaps in translational research. Crit. Rev. Oncol. Hematol., 2022, 175, 103710.
[http://dx.doi.org/10.1016/j.critrevonc.2022.103710] [PMID: 35588936]
[3]
Koedam, J.; Wermke, M.; Ehninger, A.; Cartellieri, M.; Ehninger, G. Chimeric antigen receptor T-cell therapy in acute myeloid leukemia. Curr. Opin. Hematol., 2022, 29(2), 74-83.
[http://dx.doi.org/10.1097/MOH.0000000000000703] [PMID: 35013048]
[4]
Leotta, S.; Condorelli, A.; Sciortino, R.; Milone, G.A.; Bellofiore, C.; Garibaldi, B.; Schininà, G.; Spadaro, A.; Cupri, A.; Milone, G. Prevention and treatment of acute myeloid leukemia relapse after hematopoietic stem cell transplantation: The state of the art and future perspectives. J. Clin. Med., 2022, 11(1), 253.
[http://dx.doi.org/10.3390/jcm11010253] [PMID: 35011994]
[5]
Liu, F.; Kalpage, H.A.; Wang, D.; Edwards, H.; Hüttemann, M.; Ma, J.; Su, Y.; Carter, J.; Li, X.; Polin, L.; Kushner, J.; Dzinic, S.H.; White, K.; Wang, G.; Taub, J.W.; Ge, Y. Cotargeting of mitochondrial complex I and Bcl-2 shows antileukemic activity against acute myeloid leukemia cells reliant on oxidative phosphorylation. Cancers, 2020, 12(9), 2400.
[http://dx.doi.org/10.3390/cancers12092400] [PMID: 32847115]
[6]
Martelli, A.M.; Paganelli, F.; Fazio, A.; Bazzichetto, C.; Conciatori, F.; McCubrey, J.A. The key roles of PTEN in T-cell acute lymphoblastic leukemia development, progression, and therapeutic response. Cancers, 2019, 11(5), 629.
[http://dx.doi.org/10.3390/cancers11050629] [PMID: 31064074]
[7]
Huang, Y.; Tsang, S.Y.; Yao, X.; Chen, Z.Y. Biological properties of baicalein in cardiovascular system. Curr. Drug Targets Cardiovasc. Haematol. Disord., 2005, 5(2), 177-184.
[http://dx.doi.org/10.2174/1568006043586206] [PMID: 15853750]
[8]
Li, Y.; Zhao, J.; Hölscher, C. Therapeutic potential of baicalein in alzheimer’s disease and parkinson’s disease. CNS Drugs, 2017, 31(8), 639-652.
[http://dx.doi.org/10.1007/s40263-017-0451-y] [PMID: 28634902]
[9]
Liu, H.; Dong, Y.; Gao, Y.; Du, Z.; Wang, Y.; Cheng, P.; Chen, A.; Huang, H. The fascinating effects of baicalein on cancer: A review. Int. J. Mol. Sci., 2016, 17(10), 1681.
[http://dx.doi.org/10.3390/ijms17101681] [PMID: 27735841]
[10]
Donald, G.; Hertzer, K.; Eibl, G. Baicalein--an intriguing therapeutic phytochemical in pancreatic cancer. Curr. Drug Targets, 2012, 13(14), 1772-1776.
[http://dx.doi.org/10.2174/138945012804545470] [PMID: 23140288]
[11]
Liang, W.; Huang, X.; Chen, W. The effects of baicalin and baicalein on cerebral ischemia: A review. Aging Dis., 2017, 8(6), 850-867.
[http://dx.doi.org/10.14336/AD.2017.0829] [PMID: 29344420]
[12]
Zhu, Q.J. Research advances on baicalin and baicalein as potential therapeutic agents for fibrotic disease. Zhongguo Zhongyao Zazhi, 2017, 42(7), 1271-1276.
[PMID: 29052385]
[13]
Abadi, A.J.; Zarrabi, A.; Gholami, M.H.; Mirzaei, S.; Hashemi, F.; Zabolian, A.; Entezari, M.; Hushmandi, K.; Ashrafizadeh, M.; Khan, H.; Kumar, A.P. Small in size, but large in action: microRNAs as potential modulators of PTEN in breast and lung cancers. Biomolecules, 2021, 11(2), 304.
[http://dx.doi.org/10.3390/biom11020304] [PMID: 33670518]
[14]
Agarwal, S.; Muqit, M.M.K. PTEN-induced kinase 1 (PINK1) and Parkin: Unlocking a mitochondrial quality control pathway linked to Parkinson’s disease. Curr. Opin. Neurobiol., 2022, 72, 111-119.
[http://dx.doi.org/10.1016/j.conb.2021.09.005] [PMID: 34717133]
[15]
Braglia, L.; Zavatti, M.; Vinceti, M.; Martelli, A.M.; Marmiroli, S. Deregulated PTEN/PI3K/AKT/mTOR signaling in prostate cancer: Still a potential druggable target? Biochim. Biophys. Acta Mol. Cell Res., 2020, 1867(9), 118731.
[http://dx.doi.org/10.1016/j.bbamcr.2020.118731] [PMID: 32360668]
[16]
Conciatori, F.; Bazzichetto, C.; Falcone, I.; Ciuffreda, L.; Ferretti, G.; Vari, S.; Ferraresi, V.; Cognetti, F.; Milella, M. PTEN function at the interface between cancer and tumor microenvironment: Implications for response to immunotherapy. Int. J. Mol. Sci., 2020, 21(15), 5337.
[http://dx.doi.org/10.3390/ijms21155337] [PMID: 32727102]
[17]
Wei, Y.; Ma, H.; Zhou, H.; Yin, H.; Yang, J.; Song, Y.; Yang, B. miR-424-5p shuttled by bone marrow stem cells-derived exosomes attenuates osteogenesis via regulating WIF1-mediated Wnt/β-catenin axis. Aging (Albany NY), 2021, 13(13), 17190-17201.
[http://dx.doi.org/10.18632/aging.203169] [PMID: 34229300]
[18]
Xiang, Y.; Zhang, Y.; Xia, Y.; Zhao, H.; Liu, A.; Chen, Y. LncRNA MEG3 targeting miR-424-5p via MAPK signaling pathway mediates neuronal apoptosis in ischemic stroke. Aging (Albany NY), 2020, 12(4), 3156-3174.
[http://dx.doi.org/10.18632/aging.102790] [PMID: 32065781]
[19]
Xu, S.J.; Xu, W.J.; Zeng, Z.; Zhang, M.; Zhang, D.Y. MiR-424 functions as potential diagnostic and prognostic biomarker in melanoma. Clin. Lab., 2020, 66(07/2020)
[http://dx.doi.org/10.7754/Clin.Lab.2019.190917] [PMID: 32658408]
[20]
Yalçinkaya, B. Güzel Tanoğlu, E.; Taşteki̇n, D.; Pençe, S. Role of mir-33a, mir-203b, mir361-3p, and mir-424 in hepatocellular carcinoma. Turk. J. Med. Sci., 2021, 51(2), 638-643.
[http://dx.doi.org/10.3906/sag-2004-214] [PMID: 33098283]
[21]
Yang, C.; Du, P.; Lu, W. MiR-424 acts as a novel biomarker in the diagnosis of patients with hepatocellular carcinoma. Cancer Biother. Radiopharm., 2021, cbr.2020.4141..
[http://dx.doi.org/10.1089/cbr.2020.4141] [PMID: 34287021]
[22]
Li, Z.; Wang, T.; Yu, Y. miR-424 inhibits apoptosis and inflammatory responses induced by sevoflurane through TLR4/MyD88/NF-κB pathway. BMC Anesthesiol., 2022, 22(1), 52.
[http://dx.doi.org/10.1186/s12871-022-01590-z] [PMID: 35196982]
[23]
Tanoglu, E.G. Differential expressions of miR-223, miR-424, miR-145, miR-200c, miR-139 in experimental rat chronic pancreatitis model and their relationship between oxidative stress, endoplasmic reticulum stress, and apoptosis. Iran. J. Basic Med. Sci., 2021, 24(9), 1301-1306.
[PMID: 35083018]
[24]
Fallah, A.; Alipour, M.; Jamali, Z.; Farjadfar, A.; Roshangar, L.; Partovi Nasr, M.; Hashemi, P.; Aghazadeh, M. Overexpression effects of miR-424 and BMP2 on the osteogenesis of Wharton’s jelly-derived stem cells. BioMed Res. Int., 2021, 2021, 1-10.
[http://dx.doi.org/10.1155/2021/7031492] [PMID: 34790821]
[25]
Melo Garcia, L.; Barabé, F. Harnessing macrophages through the blockage of CD47: Implications for acute myeloid leukemia. Cancers, 2021, 13(24), 6258.
[http://dx.doi.org/10.3390/cancers13246258] [PMID: 34944878]
[26]
Menter, T.; Tzankov, A. Tumor microenvironment in acute myeloid leukemia: Adjusting niches. Front. Immunol., 2022, 13, 811144.
[http://dx.doi.org/10.3389/fimmu.2022.811144] [PMID: 35273598]
[27]
Mishra, S.; Liu, J.; Chai, L.; Tenen, D.G. Diverse functions of long noncoding RNAs in acute myeloid leukemia: Emerging roles in pathophysiology, prognosis, and treatment resistance. Curr. Opin. Hematol., 2022, 29(1), 34-43.
[http://dx.doi.org/10.1097/MOH.0000000000000692] [PMID: 34854833]
[28]
Guo, C.; Yao, Y.; Li, Q.; Gao, Y.; Cao, H. Expression and clinical value of miR-185 and miR-424 in patients with acute ischemic stroke. Int. J. Gen. Med., 2022, 15, 71-78.
[http://dx.doi.org/10.2147/IJGM.S340586] [PMID: 35018114]
[29]
Chen, C.Y.; Chen, J.; He, L.; Stiles, B.L. PTEN: Tumor suppressor and metabolic regulator. Front. Endocrinol., 2018, 9, 338.
[http://dx.doi.org/10.3389/fendo.2018.00338] [PMID: 30038596]

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