GL-V9 Induce Apoptosis of CML Cells Via MAPK Signaling Pathway

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Aug 5

PMID 39100445

Authors

Fengyu Jiang

Yangyang Xue

Qin Zhang

Tonghui Ma

Yongming Li

Xiaoxuan Yu

Affiliations

Soon will be listed here.

Abstract

GL-V9, a derivative of wogonin, has shown potent antitumor effects in various cancers, yet its impact on chronic myeloid leukemia (CML) remains unexplored. In this study, we found that GL-V9 significantly decreased the viability of CML cells. Annexin V/PI staining demonstrated that GL-V9 induced apoptosis in a concentration-dependent manner. The JC-1 assay indicated a significant reduction in mitochondrial membrane potential (ΔΨm) in cells treated with GL-V9. Additionally, GL-V9 altered reactive oxygen species (ROS) levels in CML cells. Through transcriptomic sequencing and Western blot analysis, we further revealed that GL-V9 activated the MAPK pathway. These results suggest that GL-V9 is a promising therapeutic candidate for CML.

References

Bavaro L, Martelli M, Cavo M, Soverini S . Mechanisms of Disease Progression and Resistance to Tyrosine Kinase Inhibitor Therapy in Chronic Myeloid Leukemia: An Update. Int J Mol Sci. 2019; 20(24). PMC: 6940932. DOI: 10.3390/ijms20246141. View

Li L, Lu N, Dai Q, Wei L, Zhao Q, Li Z . GL-V9, a newly synthetic flavonoid derivative, induces mitochondrial-mediated apoptosis and G2/M cell cycle arrest in human hepatocellular carcinoma HepG2 cells. Eur J Pharmacol. 2011; 670(1):13-21. DOI: 10.1016/j.ejphar.2011.08.054. View

Liu X, Hu P, Li H, Yu X, Wang X, Qing Y . LW-213, a newly synthesized flavonoid, induces G2/M phase arrest and apoptosis in chronic myeloid leukemia. Acta Pharmacol Sin. 2019; 41(2):249-259. PMC: 7468447. DOI: 10.1038/s41401-019-0270-4. View

Shi X, Chen X, Li X, Lan X, Zhao C, Liu S . Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation. Clin Cancer Res. 2013; 20(1):151-63. PMC: 3938960. DOI: 10.1158/1078-0432.CCR-13-1063. View

Mayer I, Verma A, Grumbach I, Uddin S, Lekmine F, Ravandi F . The p38 MAPK pathway mediates the growth inhibitory effects of interferon-alpha in BCR-ABL-expressing cells. J Biol Chem. 2001; 276(30):28570-7. DOI: 10.1074/jbc.M011685200. View

Xing H, Ren C, Kong Y, Ni Q, Wang Z, Zhao D . Determination of GL-V9, a derivative of wogonin, in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after oral and pulmonary administration. Biomed Chromatogr. 2019; 33(8):e4556. DOI: 10.1002/bmc.4556. View

An Y, Zhang Q, Chen Y, Xia F, Wong Y, He H . Chemoproteomics Reveals Glaucocalyxin A Induces Mitochondria-Dependent Apoptosis of Leukemia Cells via Covalently Binding to VDAC1. Adv Biol (Weinh). 2023; 8(2):e2300538. DOI: 10.1002/adbi.202300538. View

Guo Y, Tian G, Chen X, Hou Y, Zhang X, Xue X . GL-V9 ameliorates liver fibrosis by inhibiting TGF-β/smad pathway. Exp Cell Res. 2023; 425(1):113521. DOI: 10.1016/j.yexcr.2023.113521. View

Schulz G, Elezkurtaj S, Bording T, Schmidt E, Elmasry M, Stief C . Therapeutic and prognostic implications of NOTCH and MAPK signaling in bladder cancer. Cancer Sci. 2021; 112(5):1987-1996. PMC: 8088911. DOI: 10.1111/cas.14878. View

10.

Banik K, Khatoon E, Harsha C, Rana V, Parama D, Thakur K . Wogonin and its analogs for the prevention and treatment of cancer: A systematic review. Phytother Res. 2022; 36(5):1854-1883. DOI: 10.1002/ptr.7386. View

11.

Lugli E, Troiano L, Ferraresi R, Roat E, Prada N, Nasi M . Characterization of cells with different mitochondrial membrane potential during apoptosis. Cytometry A. 2005; 68(1):28-35. DOI: 10.1002/cyto.a.20188. View

12.

Martinez-Castillo M, Gomez-Romero L, Tovar H, Olarte-Carrillo I, Garcia-Laguna A, Barranco-Lampon G . Genetic alterations in the BCR-ABL1 fusion gene related to imatinib resistance in chronic myeloid leukemia. Leuk Res. 2023; 131:107325. DOI: 10.1016/j.leukres.2023.107325. View

13.

Liu J, Guo Y, Zhang R, Xu Y, Luo C, Wang R . Inhibition of TRPV4 remodels single cell polarity and suppresses the metastasis of hepatocellular carcinoma. Cell Death Dis. 2023; 14(6):379. PMC: 10300155. DOI: 10.1038/s41419-023-05903-z. View

14.

Cortes J, Jabbour E, Kantarjian H, Yin C, Shan J, OBrien S . Dynamics of BCR-ABL kinase domain mutations in chronic myeloid leukemia after sequential treatment with multiple tyrosine kinase inhibitors. Blood. 2007; 110(12):4005-11. DOI: 10.1182/blood-2007-03-080838. View

15.

Hepburn A, Veeratterapillay R, Williamson S, El-Sherif A, Sahay N, Thomas H . Side population in human non-muscle invasive bladder cancer enriches for cancer stem cells that are maintained by MAPK signalling. PLoS One. 2012; 7(11):e50690. PMC: 3511341. DOI: 10.1371/journal.pone.0050690. View

16.

Cao H, Gao Y, Wang R, Guo Q, Hui H . Wogonin reverses the drug resistance of chronic myelogenous leukemia cells to imatinib through CXCL12-CXCR4/7 axis in bone marrow microenvironment. Ann Transl Med. 2020; 8(17):1046. PMC: 7575956. DOI: 10.21037/atm-20-1166. View

17.

Suttorp M, Metzler M, Millot F . Horn of plenty: Value of the international registry for pediatric chronic myeloid leukemia. World J Clin Oncol. 2020; 11(6):308-319. PMC: 7450816. DOI: 10.5306/wjco.v11.i6.308. View

18.

Lee Y, Chiou J, Chang L . AMPK inhibition induces MCL1 mRNA destabilization via the p38 MAPK/miR-22/HuR axis in chronic myeloid leukemia cells. Biochem Pharmacol. 2023; 209:115442. DOI: 10.1016/j.bcp.2023.115442. View

19.

Di Cristofano A, Niki M, Zhao M, Karnell F, Clarkson B, Pear W . p62(dok), a negative regulator of Ras and mitogen-activated protein kinase (MAPK) activity, opposes leukemogenesis by p210(bcr-abl). J Exp Med. 2001; 194(3):275-84. PMC: 2193466. DOI: 10.1084/jem.194.3.275. View

20.

Lee J, Shen P, Zhang G, Wu X, Zhang X . Dihydroartemisinin inhibits the Bcr/Abl oncogene at the mRNA level in chronic myeloid leukemia sensitive or resistant to imatinib. Biomed Pharmacother. 2012; 67(2):157-63. DOI: 10.1016/j.biopha.2012.10.017. View