Galectin-9 Inhibits Cell Proliferation and Induces Apoptosis in Jurkat and KE-37 Acute Lymphoblastic Leukemia Cell Lines Caspase-3 Activation

Overview

Journal Res Pharm Sci

Specialty Chemistry

Date 2021 Nov 11

PMID 34760009

Citations 6

Authors

Narges Zargar Balajam

Mahdi Shabani

Mahmoud Aghaei

Affiliations

Soon will be listed here.

Abstract

Background And Purpose: Acute lymphoblastic leukemia (ALL) is a type of cancer of blood and bone marrow characterized by abnormal proliferation of lymphoid progenitor cells. Galectin-9 is a tandem-repeat type galectin expressed in various tumor cells. It seems that the connection between galectin-9 and T cell immunoglobulin mucin-3 receptor acts as a negative regulator of cancer cells proliferation.

Experimental Approach: In this research, the effects of galectin-9 were investigated using MTS cell proliferation colorimetric, colony-forming, annexin V-FITC/PI, and caspase-3 assays in the Jurkat and KE-37 cell lines of ALL. Furthermore, the western blotting technique was used to evaluate the levels of apoptotic proteins such as Bax and Bcl-2 in these cell lines.

Findings/results: Our results indicated that galectin-9 can considerably reduce the cell growth and colony formation ability of both Jurkat and KE-37 cell lines in a concentration-dependent manner. Besides, galectin-9 induced apoptosis in a concentration-dependent manner in ALL cells by a mechanism associated with Bax/Bcl-2 expression and activation of the caspase-3 activation.

Conclusion And Implications: Galectin-9 inhibited the growth and proliferation of cell lines with increased programmed cell death, therefore it can be considered as a potential factor in the progression of ALL therapeutics that needs more research in this context.

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References

Fujita K, Iwama H, Sakamoto T, Okura R, Kobayashi K, Takano J . Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo. Int J Oncol. 2015; 46(6):2419-30. DOI: 10.3892/ijo.2015.2941. View

Sakhnevych S, Yasinska I, Bratt A, Benlaouer O, Goncalves Silva I, Hussain R . Cortisol facilitates the immune escape of human acute myeloid leukemia cells by inducing latrophilin 1 expression. Cell Mol Immunol. 2018; 15(11):994-997. PMC: 6207763. DOI: 10.1038/s41423-018-0053-8. View

Kuroda J, Yamamoto M, Nagoshi H, Kobayashi T, Sasaki N, Shimura Y . Targeting activating transcription factor 3 by Galectin-9 induces apoptosis and overcomes various types of treatment resistance in chronic myelogenous leukemia. Mol Cancer Res. 2010; 8(7):994-1001. DOI: 10.1158/1541-7786.MCR-10-0040. View

Jafari S, Panjehpour M, Aghaei M, Joshaghani H, Enderami S . A3 Adenosine Receptor Agonist Inhibited Survival of Breast Cancer Stem Cells via GLI-1 and ERK1/2 Pathway. J Cell Biochem. 2017; 118(9):2909-2920. DOI: 10.1002/jcb.25945. View

Oomizu S, Arikawa T, Niki T, Kadowaki T, Ueno M, Nishi N . Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner. Clin Immunol. 2012; 143(1):51-8. DOI: 10.1016/j.clim.2012.01.004. View

Folgiero V, Cifaldi L, Li Pira G, Goffredo B, Vinti L, Locatelli F . TIM-3/Gal-9 interaction induces IFNγ-dependent IDO1 expression in acute myeloid leukemia blast cells. J Hematol Oncol. 2015; 8:36. PMC: 4404691. DOI: 10.1186/s13045-015-0134-4. View

Nobumoto A, Nagahara K, Oomizu S, Katoh S, Nishi N, Takeshita K . Galectin-9 suppresses tumor metastasis by blocking adhesion to endothelium and extracellular matrices. Glycobiology. 2008; 18(9):735-44. DOI: 10.1093/glycob/cwn062. View

Jafari S, Joshaghani H, Panjehpour M, Aghaei M, Zargar Balajam N . Apoptosis and cell cycle regulatory effects of adenosine by modulation of GLI-1 and ERK1/2 pathways in CD44 and CD24 breast cancer stem cells. Cell Prolif. 2017; 50(4). PMC: 6529124. DOI: 10.1111/cpr.12345. View

Kashio Y, Nakamura K, Abedin M, Seki M, Nishi N, Yoshida N . Galectin-9 induces apoptosis through the calcium-calpain-caspase-1 pathway. J Immunol. 2003; 170(7):3631-6. DOI: 10.4049/jimmunol.170.7.3631. View

10.

Paul S, Kantarjian H, Jabbour E . Adult Acute Lymphoblastic Leukemia. Mayo Clin Proc. 2016; 91(11):1645-1666. DOI: 10.1016/j.mayocp.2016.09.010. View

11.

Madireddi S, Eun S, Mehta A, Birta A, Zajonc D, Niki T . Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9. J Immunol. 2017; 199(8):2721-2728. PMC: 5659314. DOI: 10.4049/jimmunol.1700575. View

12.

Zhang Z, Dong J, Chen Y, Wang X, Li C, Wang J . Galectin-9 acts as a prognostic factor with antimetastatic potential in hepatocellular carcinoma. Asian Pac J Cancer Prev. 2012; 13(6):2503-9. DOI: 10.7314/apjcp.2012.13.6.2503. View

13.

Tadokoro T, Morishita A, Fujihara S, Iwama H, Niki T, Fujita K . Galectin-9: An anticancer molecule for gallbladder carcinoma. Int J Oncol. 2016; 48(3):1165-74. DOI: 10.3892/ijo.2016.3347. View

14.

Tadokoro T, Fujihara S, Chiyo T, Oura K, Samukawa E, Yamana Y . Induction of apoptosis by Galectin-9 in liver metastatic cancer cells: In vitro study. Int J Oncol. 2017; 51(2):607-614. DOI: 10.3892/ijo.2017.4053. View

15.

Wang Z, Zhu J, Gu H, Yuan Y, Zhang B, Zhu D . The Clinical Significance of Abnormal Tim-3 Expression on NK Cells from Patients with Gastric Cancer. Immunol Invest. 2015; 44(6):578-89. DOI: 10.3109/08820139.2015.1052145. View

16.

Kageshita T, Kashio Y, Yamauchi A, Seki M, Abedin M, Nishi N . Possible role of galectin-9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance. Int J Cancer. 2002; 99(6):809-16. DOI: 10.1002/ijc.10436. View

17.

Irie A, Yamauchi A, Kontani K, Kihara M, Liu D, Shirato Y . Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer. Clin Cancer Res. 2005; 11(8):2962-8. DOI: 10.1158/1078-0432.CCR-04-0861. View

18.

Zhu C, Anderson A, Kuchroo V . TIM-3 and its regulatory role in immune responses. Curr Top Microbiol Immunol. 2010; 350:1-15. DOI: 10.1007/82_2010_84. View

19.

Takano J, Morishita A, Fujihara S, Iwama H, Kokado F, Fujikawa K . Galectin-9 suppresses the proliferation of gastric cancer cells in vitro. Oncol Rep. 2016; 35(2):851-60. DOI: 10.3892/or.2015.4452. View

20.

Jafari S, Nazri A, Shabani M, Zargar Balajam N, Aghaei M . Galectin-9 induces apoptosis in OVCAR-3 ovarian cancer cell through mitochondrial pathway. Res Pharm Sci. 2019; 13(6):557-565. PMC: 6288986. DOI: 10.4103/1735-5362.245967. View